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Abstract

Background:

The population in Latin America and Caribbean (LAC) has experienced a major demographic transition with increased numbers of older adults (OA). This change brings opportunities in the public health sector to implement health prevention interventions and delay the onset of geriatric syndromes. Micronutrients play an important role in the maintenance of biological function which contributes to longevity. Micronutrient deficiencies (MD) in OA increase the risk for onset of chronic comorbidities and geriatric syndromes.

Aim:

To review and summarize the existing data on micronutrient status in OA in the LAC region and discuss the gaps and challenges in public health approaches to address deficiencies.

Methods:

Literature review in Medline for records describing nutritional biomarkers in older adults (≥ 60y) from community dwelling and population-based studies in LAC.

Results:

Few countries (including Chile, Ecuador, Costa Rica, Brazil, and Mexico) have documented one or more nutritional deficiencies for OA in national health surveys, however across the entire region, evidence of micronutrient levels is scarce. Some surveys have documented a high prevalence and large heterogeneity in the prevalence of vitamin D followed by B12 deficiency, being the 2 MDs most studied due their effects on cognition, frailty, and bone mineral density in the OA population. Other MD including C, E, A, copper, zinc, iron, and selenium have also been reported.

Conclusion:

Information on the micronutrient status in OA from LAC is poorly documented. Research and capacity building initiatives in the region are crucial to develop tailored strategies that address the specific nutritional needs and challenges faced by the ageing population in Latin America.

Plain language title

Micronutrients Deficiencies in Older Adults in Latin American

Plain language summary

For the first time, there are more older adults (OA) than children worldwide. In the Latin America and Caribbean (LAC) region, OA represents 13.2% of the population, and it is projected to increase to 30% (220 millions) by 2030. This demographic shift represents an opportunity in the public health sector to implement health prevention strategies and public health policies to delay the onset of geriatric syndromes in the younger generation. Vitamins and minerals (micronutrients) are necessary in our body to maintain biological function. Deficiencies in older ages have been associated with the onset of geriatric syndromes (such as sarcopenia, frailty, cognitive impairment, and falls, among others). Therefore, it is relevant to understand the magnitude and distribution of micronutrient deficiencies in OA in the LAC region. This will help to inform decision-makers to further implement early actions to maintain good nutrition and health status in the population. In this narrative review, we highlight that few countries in the LAC region documented one or more nutritional deficiencies for OA in their national health surveys. Across the entire region, evidence of micronutrient levels in OA is scarce. Vitamin D and vitamin B12 are the 2 most reported micronutrients in the OA population. Research and capacity-building in the region are crucial to develop tailored strategies to address specific nutritional needs and challenges faced by the aging population in Latin America.

Keywords

micronutrient deficiency ageing older adults Latin America

Introduction

The demographic transition in most low- and middle-income countries (LMIC) has experienced rapid changes in the population age structure.¹ For the first time, there are more older adults (OA) than children worldwide.² The number of OA ≥60 years old in the Latin America and Caribbean countries (LAC) is around 88.6 million, representing 13.2% of population. The OA population in this region is projected to increase to 114.9 million (16.5%) by 2030, and to 220 million (30%) by 2060. By the end of this century (2100), OA aged 80 years and over will be the only population group that will continue to grow at the regional level.³ All these projections represent an opportunity to develop public policies in anticipation of these population changes, to address inequalities in the public health sector,⁴ and to implement preventive strategies to achieve healthy aging. At the same time, these predicted population shifts bring challenges in currently fragmented and segmented health care sectors when it comes to managing geriatric syndromes (such as loss of autonomy, frailty, sarcopenia, and dementia, among others), providing quality care and addressing overall inequity in access to health care without action at the public health level.⁵

The change in the life expectancy at birth has increased an average of 6.9 years in the Latin American region over the last 30 years. In part, this is a result of the success of public health policies implemented several decades ago that focus on the early stages of life, including policies addressing micronutrient deficiencies (MD) in childhood (+0.3 years gained) and maternal and neonatal health coverage improvements (Figure 1).⁶

Figure 1.

Change in sub-region life expectancy at birth from 1990 to 2019 in both sexes by broad cause group in selected regions. AIDS, acquired immunodeficiency syndrome; Am, America; CKD, chronic kidney disease; HI, high income; N, North; Pac, Pacific; S, south; STD, sexually transmitted infections; TB, tuberculosis; Trop, tropical; W, western; NTD, nontransmissible diseases.

Micronutrients such as vitamin B12, folate, vitamin D, iron, magnesium, and zinc (among others) play an important role in the maintenance of biological function, immunity, and functionality across the life span including in OA, which together contribute to longevity.⁷ As a result of physiological changes that occur during the aging process,⁸ MDs are common in OA and may pose a risk in the onset of chronic comorbidities, infection, and geriatric syndromes.⁹ The causes of MD in OA are complex and quite often multifactorial and frequently relate to dietary deficiencies, malabsorption syndromes, polypharmacy, and comorbidities. Having a better understanding the complexities of MD in OA is essential to enable well designed preventive health interventions for OA to maximize functional independence and quality of life, in alignment with the UN Decade of healthy aging.¹⁰

The United Nations has declared 2021 to 2030 the “decade of healthy aging.” As such, this represents an opportunity to focus efforts on improving quality of life for OA and to maximize our later years in a sustainable and healthy way, to benefit both for current and future generations.¹⁰ Ongoing public health efforts in the region are addressing MD and anemia in children and women, with known deficiencies in indigenous populations and those living in poverty and in rural areas. However, our understanding of MD in OA is less well documented.¹¹ In this narrative review, we highlight what we know about common nutritional deficiencies and their role in the health of older Latin American adults. We discuss the gaps and challenges to address these deficiencies to achieve healthy aging.

Methods

A literature review was conducted in MEDLINE (PubMed) for records describing nutritional biomarkers and micronutrient deficiencies in OA (≥60 years) in outpatient clinical and field settings (community and population-based studies) where the crude prevalence was reported in the Latin American region, in the period 2000 to 2022. We excluded case reports, duplicates, theses, and studies that did not report prevalence, hospital-based settings and, where OA were in residential health care settings for specific medical conditions (heart diseases, hip fractures, COVID-19, etc).

Results and Discussion

Commonly Measured Micronutrient Biomarkers

A total of 28 studies reported one or more MDs in OA in Latin America in 8 Latin American countries (Table 1). National health surveys and aging surveys conducted in Chile, Ecuador, Brazil, Costa Rica, and Mexico reported MD in their OA populations. In addition, MD prevalence was reported through local (community-based) studies in the same countries, with the addition of Argentina, Peru, and Venezuela.

Table 1.

Summary of Studies Documenting the Prevalence of Micronutrient Deficiencies in Older Latin Adults.

Micronutrient^a	Country	Year of study	Definition	Age group	Prevalence %	Study setting	Ref
Vitamin B12	Brazil	2011	B12 (<140 pg/mL)	≥60 y	17.4	Community	¹²
	Chile	2000^b	B12 (<74 pmol/L)	Women ≥60 y	2.8	Urban community	¹³
			B12 (<74 pmol/L)	Men ≥60 y	6.5
			B12 (<148 pmol/L)	Women ≥60 y	30.9
			B12 (<148 pmol/L)	Men ≥60 y	51.1
		2005-2008	B12 (<148 pmol/L)	≥65 y	12.0	Community	¹⁴
				Women ≥65 y	9.0
				Men ≥65 y	18.2
			B12 (148-221 pmol/L)	≥65 y	13.4
				Women ≥65 y	10.9
				Men ≥65 y	18.8
		2009-2010	B12 (≤200 pg/mL)	≥60 y	8.1	Population based	¹⁵
				Women ≥60 y	9.2
				Men ≥60 y	6.6
		2020	B12 (≤200 pg/mL)	≥60 y	16.1	Hospital based	¹⁶
	Costa Rica	2008-2009	B12 (<193pg/mL)	≥65 y	5.3	Population based	¹⁷
	Ecuador	2003-2004	B12 (<185 pmol/L)	Women ≥65 y	19.6	Peri-urban Community	¹⁸
		2003-2004	B12 (<185 pmol/L)	Men ≥65 y	20.5	Peri-urban Community	¹⁸
		2009-2010	B12 (≤350 pg/mL)	Women ≥60 y	30.6	Population based	¹⁹
		2009-2010	B12 (≤350 pg/mL)	Men ≥60 y	47.8	Population based	¹⁹
	Mexico	2003-2004	B12 (<150 pmol/L)	≥60 y	30.0	Urban Community	²⁰
	Mexico	2015	B12 (<−0.5 SD)	≥60 y	9.0	Urban-Community	²¹
	Peru	2014-2020	B12 (<80 pg/mL)	≥60 y	21.0	Hospital based	²²
Folate	Chile	1999-2000	Folate (<6.8 nmol/L)	≥70 y	1.8	Community	²³
		2000	Folate (<7 nmol/L)	Women ≥60 y	33.1	Community	¹³
		2000	Folate (<7 nmol/L)	Men ≥60 y	50.5	Community	¹³
		2009-2010	Folate (≤4.4 µg/L)	≥60 y	0.3	Population based	¹⁵
				Women ≥60 y	0.4
				Men ≥60 y	0.1
	Costa Rica	2008-2009	Folate (≤6.0 ng/mL)	≥65 y	1.4	Population based	¹⁷
	Ecuador	2003-2004	Folate (<11.3 nmol/L)	Women ≥65 y	27.4	Peri-urban Community	¹⁸
	Ecuador	2003-2004	Folate (<11.3 nmol/L)	Men ≥65 y	37.0	Peri-urban Community	¹⁸
	Mexico	2003-2004	Folate (<3 ng/mL)	≥60 y	0.0	Community	²⁰
	Mexico	2015	Folate (<4 ng/mL)	≥60 y	0.0	Community	²¹
	Peru	2014-2020	Folate (<3 ng/dL)	≥60 y	1.7	Hospital based	²²
	Venezuela	2007	Folate (<3 ng/mL)	≥60 y	12.5	Community	²⁴
Vitamin D (25(OH)D)	Argentina	2004	Deficiency < 10 ng/mL	≥65 y	North = 2	Urban community	²⁵
					Center = 11
					South = 14
			Insufficiency 10-20 ng/mL		North = 52
					Center = 64
					South = 87
			Hypovitaminosis 20-40 ng/mL		North = 46
					Center = 35
					South = 13
	Brazil	2000-2001	Deficiency <25 nmol/L	>65 y	15.4	Urban community	²⁶
		2000-2001	Insufficiency 25-50 ng/mL	>65 y	41.9	Urban community	²⁶
		2000-2017	Deficiency <20 ng/mL	≥60 y	41.53	Meta-analysis	²⁷
		2000-2017	Insufficiency 20-30 ng/mL	≥60 y	45.85	Meta-analysis	²⁷
		2015-2016	insufficiency and deficiency <50 nmol/L	Women ≥60 y	60	Population based cohort study	²⁸
	Chile	2006	Deficiency <20 ng/mL	≥60 y	70.2	Community	²⁹
				Women ≥60 y	82.5
				Men ≥60 y	55.3
			Insufficiency 20-29.9 ng/mL	≥60 y	24
				Women ≥60 y	14
				Men ≥60 y	36.2
		2016-2017	Deficiency <20 ng/mL	≥65 y	59.5	Population based	³⁰
		2016-2017	Insufficiency ≥20 ng/mL	≥65 y	40.5	Population based	³⁰
	Ecuador	2003-2004	Deficiency <20 ng/mL	Women ≥65 y	9.4	Community	¹⁸
		2003-2004	Deficiency <20 ng/mL	Men ≥65 y	18.8	Community	¹⁸
		2009	Deficiency <20 ng/mL	≥60 y	21.6	Population based	³¹
				Women ≥60 y	29.6
				Men ≥60 y	11.5
			Insufficiency < 30 ng/mL	≥60 y	67.8
				Women ≥60 y	77.4
				Men ≥60 y	55.9
	Guatemala	2010	Deficiency <50 nmol/L	≥60 y	50.0	Community	³²
	Guatemala	2010	Insufficiency 50-80 nmol/L	≥60 y	46.3	Community	³²
	México	2012	Deficiency ≤20 ng/mL	≥60 y	36.9	Population based cohort study	³³
				Women ≥60 y	46.8
				Men ≥60 y	26.3
		2015	Deficiency <50 nmol/L	≥60 y	9.7	Urban Community	²¹
		2020	Deficiency <20 ng/mL	≥60 y	34.2	Community	³⁴
		2020	Insufficiency 20-30 ng/mL	≥60 y	41.1	Community	³⁴
		2021	Deficiency <40 nmol/L	Women ≥60 y	49.1	Community	³⁵
	Puerto Rico	2011	Deficiency <20 ng/mL	≥ 60 y	19.5	Community	³⁶
	Puerto Rico	2011	Insufficiency 20-30 ng/mL	≥ 60 y	43.4	Community	³⁶
	Tobago	1997-2003	Deficiency <20 ng/mL	≥60 y	2.8	Population-based cohort study	³⁷
	Tobago	1997-2003	Insufficiency 20-29 ng/mL	≥60 y	24.1	Population-based cohort study	³⁷
Iron	Brazil	2015	Depleted iron stores = s-ferritin <15 μg/L adjusted by CRP	≥60 y	1.9	Population-based	³⁸
				Women ≥60 y	1.8
				Men ≥60 y	2
	Ecuador	2003-2004	s-Iron < 8.95 μmol/L women	Women ≥65 y	5	Urban community	¹⁸
	Ecuador	2003-2004	s-Iron < 11.6 μmol/L men	Men ≥65 y	4	Urban community	¹⁸
	Mexico	2012	S-ferritin < 15 μg/L adjusted by CRP	≥60 y	4.2	Population based	³⁹
				Women ≥60 y	1.3
				Men ≥60 y	4
		2015	S-ferritin < 15 adjusted by CRP and AGP & sTfR > 28 nmol/L	≥60 y	5.1	Urban community	²¹
		2018	S-ferritin <15 μg/L adjusted by CRP	≥60 y	5	Population-based	⁴⁰
				Men ≥60 y	4.4
				Women ≥60 y	5.4
Vitamin A	Chile	2000	Retinol (<0.35 µ mol/L)	Women ≥60 y	15.9	Community	¹³
	Chile	2000	Retinol (<0.35 µ mol/L)	Men ≥60 y	13.7	Community	¹³
	Ecuador	2003-2004	Retinol (<1.05 µmol/L)	Women ≥65 y	4.1	Peri-urban Community	¹⁸
	Ecuador	2003-2004	Retinol (<1.05 µmol/L)	Men ≥65 y	0.8	Peri-urban Community	¹⁸
	Mexico	2015	Retinol (≤20 µg/dL)	≥60 y	3.4	Urban-Community	⁴¹
Copper	Chile	2000	Copper (<11.0 µ mol/L)	Women ≥60 y	5.1	Community	¹³
	Chile	2000	Copper (<11.0 µ mol/L)	Men ≥60 y	6.5	Community	¹³
	Ecuador	2003-2004	Copper (<13.2 µmol/L)	Women ≥65 y	12.4	Peri-urban Community	¹⁸
	Ecuador	2003-2004	Copper (<13.2 µmol/L)	Men ≥65 y	16.7	Peri-urban Community	¹⁸
Vitamin E	Ecuador	2003-2004	Vitamin E (<11.6 µmol/L)	Women ≥65 y	9.4	Peri-urban Community	¹⁸
Vitamin E	Ecuador	2003-2004	Vitamin E (<11.6 µmol/L)	Men ≥65 y	18.8	Peri-urban Community	¹⁸
Vitamin C	Ecuador	2003-2004	Vitamin C (<11.4 µmol/L)	Women ≥65 y	32.6	Peri-urban Community	¹⁸
Vitamin C	Ecuador	2003-2004	Vitamin C (<11.4 µmol/L)	Men ≥65 y	59.8	Peri-urban Community	¹⁸
Selenium	Costa Rica	2008-2009	Selenio (<60 µ/L)	≥65 y	29.0	Population based	¹⁷
Zinc	Brazil	2018-2019	Zinc (<70 µg/dL)	≥60 y	3.9	Community	⁴²
	Ecuador	2003-2004	Zinc (<10.7 µmol/L)	Women ≥65 y	45.4	Peri-urban Community	¹⁸
	Ecuador	2003-2004	Zinc (<10.7 µmol/L)	Men ≥65 y	41.3	Peri-urban Community	¹⁸

Abbreviation: CRP, C-reactive protein; AGP, Alpha(1)-Acid glycoprotein; sTfR: serum soluble transferrin receptor.

^a Data on micronutrient are ordered according to its description in the manuscript.

^b Not specified. Year of publication.

Vitamin B12 and Folate Deficiency

Ecuador,¹⁹ Chile,¹⁵ and Costa Rica¹⁷ reported the prevalence of low vitamin B12 levels in OA from representative surveys (Table 1), with a large heterogeneity in the prevalence of Vitamin B12 deficiency (B12D) by sex, and when data was gathered from local studies.

The active forms of Vitamin B12 are methylcobalamine and adenosylcobalamin, they act as cofactors in 2 separate metabolic reactions, with cytosolic methionine synthase and mitochondrial methymalonyl CoA mutase. The disruption of either of these reactions can lead to B12 deficiency. In B12D, decreased levels of adenosylcobalamin lead to an increase in methylmalonyl-CoA, which affects synthesis of neuronal myelin in the developing central nervous system; while decreased levels of methylcobalamine leads to the functional deficiency of folate and accumulation of homocysteine.^43,44 B12 metabolism is linked with folate-mediated one-carbon metabolism due to the utilization of 5-methyltetrahydrofolate as a methyl donor.⁴⁴ Both, B12 and folate deficiency (FD), affect DNA synthesis with resulting macrocytic anemia. B12D increases cellular inflammation (hypersegmented neutrophils) and the synthesis of intermediate metabolites such as homocysteine and methylmalonic acid (MMA).⁴⁴ Increased levels of homocysteine and MMA can result in severe damage to the brain and spinal cord, particularly in the corticospinal and spinocerebellar tracts, resulting in ataxia, neuropathy and in later life, cognitive decline.⁴⁵ There are numerous studies exploring B12D in older populations due to the association with cognitive decline, impaired executive function, and the risk of dementia. The OA population is at higher risk of B12D due to malabsorption secondary to gastric atrophy, diminished intrinsic factor and hydrochloric acid.⁴⁶ In Latin America, B12D has been widely studied in the Chilean population, with the Government responding with public health initiatives to address deficiencies.⁴⁷ Along with Chile,⁴⁸ Ecuador,¹⁹ and Peru²² have also documented the role of subclinical B12 deficiency on cognitive function in OA, with contradictory findings. In a cross-sectional study of older Cuban adults, higher homocysteine levels and FD but not B12D were associated with mild cognitive impairment.⁴⁹ Daily fluctuations of B12 levels in serum may not properly reflect the true B12 status. What might be useful are combinatory approaches for measuring multiple, related indicators of VB12 levels in OA. For example, measuring the intermediate metabolites homocysteine and MMA, or others involved in the transport of B12 such as holotranscobalamin, which when combined, might improve sensitivity in the diagnosis of B12D.⁵⁰

Since the introduction of the mandatory folate fortification in wheat and corn flour in some Latin American countries,⁵¹ FD has dropped below 1% prevalence in OA. As such, FD is no longer considered an ongoing public health challenge in those countries.⁵¹ Only a few studies have documented FD in OA. However, supraphysiological levels of folate have been reported in older Chilean and Mexican populations (Table 2). Elevated folate levels have been implicated in exacerbating B12D.⁵² The mechanism of folate-VB12 interaction is not well understood; however, there is some evidence that high folate levels (HFL) decrease the effectivity of vitamin B12 treatment in B12D.⁵³ In some studies, HFL and low vitamin B12 has been linked to impaired cognition in OA,^54,55 but in other studies, authors have documented high folate levels associated with higher score in cognitive function, independent of B12 levels.^56,57 More research is needed to better understand how low levels of vitamin B12 (subclinical deficiency) interact with high levels of folate in the progression of cognitive decline.

Table 2.

Supraphysiological Levels of Folate and Iron in Older Population From Selected Studies in the Latin American Region.

Micronutrient	Country	Year of study	Definition	Age group	Prevalence %	Study setting	Ref
Folate	Chile	2009-2010	>20 µg/L	≥65 y	48.6	Population based	¹⁵
				Women ≥65 y	48.5
				Men ≥65 y	48.7
	Mexico	2003-2004	Folate >17 ng/mL	≥60 y	62	Urban-Community	²⁰
	Mexico	2015	Folate >17 ng/mL	≥60 y	5.1	Urban-Community	²¹
Iron	Brazil	2015	s-ferritin>150 μg/L	Women ≥60 y	NO^a	Population based	³⁸
	Brazil	2015	s-ferritin>200 μg/L	Men ≥60 y	35.8	Population based	³⁸
	Mexico	2015	s-ferritin>150 μg/L women and >200 μg/L in men	≥60 y	29.8	Urban-Community	²¹
	Mexico	2015	s-ferritin>350 μg/L adjusted by CRP	≥60 y	7.35	Urban-Community	²¹

Abbreviation: CRP, C-reactive protein.

^a NO: no observations.

Vitamin D Deficiency

Brazil,²⁸ Chile,³⁰ Ecuador,⁵⁸ and Mexico³³ reported the prevalence of low vitamin D levels in OA from representative surveys (Table 1). Vitamin D (VD) status is the most reported micronutrient in the LAC region. Both, VD insufficiency and deficiency (VDD) are highly prevalent in OA, reaching a prevalence (25[OH]D <20 ng/mL) higher than 50% in Brazil²⁸ and Chile,³⁰ which is comparable with other LMIC.⁵⁹ Most studies have used 25[OH]D levels for classifying VDD in OA populations.⁶⁰

At the community level, the VDD prevalence in OA varied, probably due to sample characteristics, seasonality (more prevalent in winter), and latitude (Table 1). Two metanalyses^27,61 have been conducted to estimate VDD in the region, showing a prevalence of 41.5% (95%CI: 27.6, 55.4) in older Brazilian adults, and 34.8% (95%CI: 29.7, 40.2) in all age groups in the South-American Region.

Sun exposure is the primary source of vitamin D for the human body⁶⁰ with dietary intake of VD making a smaller contribution to VD status.^62,63 Advanced age has been associated with a lower capacity for the body to synthesize vitamin.^64,65 In addition, OA with chronic comorbidities (such as obesity, diabetes, kidney disease)⁶⁶ have impaired absorption and metabolism of vitamin D.^67,68 Therefore, supplements of VD are often required to reach the daily intake recommendation.

Vitamin D (along with vitamin A) regulates gene expression and acts as transcription factor for multiple genes that modulate the immune response.^69,70 VD is essential for maintaining bone, muscle health, and erythropoiesis, therefore, its deficiency can have a significant impact on quality of life for OA.^71,72

Vitamin D deficiency increases the risk of osteoporosis, bone fractures, type 2 diabetes, respiratory diseases, sleep disorders, depression, impaired cognition, cardiovascular disease, autoimmune diseases, and some types of cancer.^69,72,73 Older adults with VDD have a higher risk of falls, sarcopenia, and decreased functional capacity, which can in turn lead to increased frailty, dependence, and disability.^71,73

Recent systematic reviews and meta-analysis has suggested a correlation between low Vitamin D and impaired cognitive function.^72,74,75 Evidence from a number of observational studies is contradictory, possibly due to residual confounding. For instance, in one study, VDD was not associated with cognitive function in OA from Ecuador.¹⁹ In other studies, metanalysis exploring supplementation of VD did not show any effect on cognition or depression.^76,77

During the COVID-19 pandemic, VD was studied in several populations due its role in strengthening the immune system by modulating the inflammatory response during infection. For all age groups, including OA, VDD was associated with COVID-19 severity and mortality^78,79 Supplementation with VD may contribute to the prevention and management of COVID-19 infection.⁷⁹ Nonetheless, a causal relationship between vitamin D status, VD supplementation, and COVID-19 (incidence, severity and progression) has not been established due to methodological differences in those studies.

Iron Deficiency

Information about iron deficiency (ID) in OA is scant. In those studies that report it (Mexico and Brazil), the prevalence of ID was around 5% or less.^38,40 Low iron stores, and ID, are typically defined by measuring s-ferritin levels (an acute phase protein). However, established thresholds for defining ID are based on adult populations that do not take into account any normative changes that might occur in OA.⁸⁰ The diagnosis of ID is challenging in OA since low grade inflammation secondary to the aging process (inflammaging), infection and chronic comorbidities may all increase ferritin levels. Functional ID can be the result of inflammation (for example caused by infection, cancer, rheumatoid arthritis, autoimmune disease or, chronic disease),⁸¹ as a result of increased hepcidin, a protein that blocks iron export from ferroportin in the epithelial cells thereby limiting iron availability in the bone marrow. In the presence of infection, the body reduces circulating iron in an attempt to combat pathogens.⁸² Consequently, prolonged iron deprivation (referred to as functional iron deficiency) can lead to anemia of chronic diseases or anemia of inflammation.⁸³ To improve diagnosis specificity for ID, the use of s-ferritin as an indicator should be used in conjunction with inflammatory biomarkers to generate a more reliable indicator of overall iron status.⁸⁴ Iron deficiency and anemia are detrimental to health. Iron deficiency is the main cause of anemia in younger populations in LMIC⁸⁵ and it is estimated to be the second leading cause in OA.⁸⁶ Few studies have documented the causes of anemia in OA in Latin America.^21,87,88

Iron deficiency leads to poor quality of life and disability.⁸⁹ It has also been established that ID anemia (IDA) increases the risk of morbidity and mortality in OA.^90,91 The causes of ID in OA are usually associated with gastrointestinal blood loss (caused by varices in portal hypertension, gastritis, ulcers, inflammatory bowel diseases, among others) which can lead to IDA. In addition, alcohol abuse, malnutrition, and chronic diseases as chronic renal failure and inflammatory diseases can also result in ID and lead to IDA.

Iron is a trace mineral essential for maintaining normal physiological processes involved in the electron transport chain, mitochondrial respiration, DNA synthesis, and synthesis of heme, myelin, and neurotransmitters. Due to its role in redox activity, iron is tightly regulated in the body. Excessive iron results in catalyzed oxidative reactions that generate reactive oxygen species (ROS). ROS (oxidative stress) causes DNA damage, lipid peroxidation, and aberrant posttranslational modification of proteins.⁹² In mitochondria, energy production generates ROS. Iron utilization in the mitochondria requires proteins to regulate iron homeostasis (frataxin, mitoferrin) since it is vulnerable to iron-induced oxidative stress. The loss of mitochondrial iron homeostasis in combination with iron accumulation, may contribute to mitochondrial decay, which is characteristic of aging.⁹³ These mitochondrial changes may be involved in the pathogenesis of age-related neuro-muscular degeneration (muscle atrophy, sarcopenia).⁹³ As part of normal aging, the central nervous system shifts into a pro-inflammatory state, with increases in glial cells numbers and increased permeability of the blood–brain barrier. These ageing-related changes can lead to regional increases in brain iron⁹⁴ which in turn has been correlated with the presence of neurodegeneration.^95,96 To date, this correlation has not been shown to be causal.^95,97 Evidence from observational studies linked high ferritin levels and neurodegeneration has been inconclusive. High ferritin levels have been linked to cardiovascular disease, diabetes, and increased mortality in the older adult population.^98,99 Two studies in the Latin American region (Brazil and Mexico) reported a higher prevalence of increased ferritin levels in OA. To better understand the nature of the relationship (correlation, cause, or consequence) between increased iron levels and aging, more research in the LAC region is needed.

Vitamin A Deficiency

Few countries (Chile, Mexico, and Ecuador) have reported the prevalence of Vitamin A (VA, also known as retinol) deficiency in older Latin America population, with estimates of less than 5% prevalence (Table 1).

Vitamin A is a liposoluble vitamin that plays an important role in gene expression, transcription, stem cell differentiation, cell proliferation, vision, growth, maintenance of epithelial cellular integrity, and immune function.¹⁰⁰ Vitamin A deficiency leads to a depleted immune system, night blindness, altered bone metabolism,¹⁰¹ and increased risk of respiratory infections.¹⁰² Retinoic acid (the main metabolite of VA) has been reported to have neuroprotective effects in the amyloid signaling cascade, as well a role in synaptic plasticity, associated with memory.^103,104 We previously reported a cross-sectional association of low serum retinol with lower verbal fluency in older Mexican adults.⁴¹ In older Cuban adults, vitamin A deficiency was cross-sectionally associated with increased risk for mild cognitive impairment.⁴⁹ Moreover, higher retinol levels have been associated with higher adverse events in other OA populations (lower bone density, cardiovascular risk, and mortality).^101,102

Copper, Zinc, Vitamin E, Vitamin C Selenium, and Magnesium Deficiencies

There are very few reports of levels of copper, zinc, vitamin E, vitamin C, or selenium in Latin American populations. One study in a subset of OA Ecuadorians in a low-income peri-urban community in Quito, documented a cross-sectional association of low levels of vitamin C, E, copper, and zinc with anemia and respiratory infections via negative impacts on immune function.¹⁸ Costa Rica is the only country in the region that has published evidence of low levels of s-selenium in OA.¹⁷ Deficiency of all these micronutrients in OA from other populations has been associated with a deprived immune system,¹⁰⁵ oxidative stress,¹⁰⁶ anemia,¹⁰⁷ cardiovascular disease,¹⁰⁸ and impaired cognitive function,¹⁰⁹ among others.

Zinc plays a pivotal role in maintaining health and well-being in OA. In the region, Brazil⁴² and Ecuador¹⁸ are the only countries that have reported serum zinc concentrations in OA. Low zinc levels affect T cells and cytokines activity, wich impairs the immune response.¹¹⁰ Consequently, OA with zinc deficiency (ZD) might experience a higher incidence and longer duration of respiratory diseases, as shown in the study with Ecuadorian OA.¹⁸ Intervention studies with zinc supplementation have shown that an increase in serum zinc levels boosts T cells, enhancing immune system function.¹¹¹ Zinc is also involved in preserving bone integrity by controlling bone resorption and deposition, with low levels of zinc being a risk factor for osteoporosis.¹¹² Furthermore, the brain contains the highest zinc concentration compared to other organs. Zinc acts as a modulator for neurotransmitters such as glutamate, and γ-aminobutyric acid (GABA), is involved in glycinergic synaptic transmission.¹¹³ ZD can impair enzyme metabolism in the brain, leading to an accumulation of pathological proteins linked to Alzheimer’s disease.¹¹⁴ In older Brazilian adults, ZD has been associated with cognitive decline.⁴²

So far, no countries in the region have studied the role of Magnesium (Mg) and health in OA. Mg has a pivotal role in aging and longevity since it modulates both the innate and the acquired immune response acting as anti-ROS preserving genomic stability,¹¹⁵ and as a cofactor for multiple proteins reactions (eg. muscle synthesis ATP, vitamin D synthesis among others).¹¹⁶ In the brain, Mg preserves the integrity and stability of the cell membrane, reduces neuroinflammation, is involved in neural maturation and clearance the proteins and toxins from the brain.¹¹⁷ Deficits of Mg have been associated with insulin resistance, diabetes, cardiovascular disease, cancer, hypertension, asthma, psychiatric disorders, osteoporosis, cognitive decline, and Alzheimer´s disease.^116,118
-120 Epidemiological studies in OA (from North America, Japan and Australia) have shown that low intakes of Mg are associated with a higher risk of cognitive decline and dementia of all types, including vascular dementia.^121
-123 Further research is needed to better understand the role of Zn, Mg, and others MD in health and disease, in order to design effective strategies to achieve a healthy aging in the region.

The Gaps and Challenges

To date, information on the micronutrient status in older populations is scarce in most Latin American countries. Information that is reported comes from representative surveys and local studies (which are not representative of the national population within each country). Most of the aging surveys used in Latin America do not collect enough information about nutritional biomarkers to accurately characterize the micronutrient status of the population, and these biomarkers are not routinely measured. The assessment of the micronutrient status at a population level in OA requires investment, a coordinated approach to data collection, as well the appropriate equipment and certified laboratories to process biological samples. Moreover, there are no universally agreed serum/plasma micronutrient thresholds to define deficiency in OA.¹²⁴ A variety of cut-off points to define micronutrient deficiencies are used which makes comparison across the Latin American region difficult. Some existing thresholds used to define “deficiency” are based on data from younger adults and do not consider age-related changes. This brings challenges when interpretating the “deficiency status” in this age group, including in the identification of deficiencies in the subclinical range, which might represent the best opportunity for timely intervention. Malabsorption syndromes, polypharmacy, and chronic comorbidities are common conditions of OA, which in themselves can exacerbate micronutrient deficiencies. Additionally, the effect of low-grade inflammation during aging might mask underlying deficiencies in micronutrients such as retinol, iron, and zinc. With all of this in mind, it is likely that micronutrient deficiency is underestimated in OA in LAC. Micronutrient deficiencies tend to disproportionately affect underrepresented and vulnerable groups, such as black, indigenous, rural populations, and those with lower socioeconomic status, where health inequities persist.¹²⁵ More research is needed to better understand the long-term risk of MD and the inherent inequities in the LA region, before it can be effectively addressed.¹²⁵

The lack of information about MD in most countries across the region make it challenging to respond adequately and comprehensively to the UN declaration of the decade of healthy aging. Regular data collection is crucial for surveillance of micronutrient levels in OA population. In addition, longitudinal studies in OA are needed to accurately describe trends in MD and to identify the window of opportunity where nutritional intervention would be most effective. Revising and agreeing on recommendations of micronutrient levels in OA, and including consensus criteria for diagnosing deficiencies, are both needed to allow comparison within and between countries as well as to evaluate the response to any interventions. Without this, the existing gaps in our understanding continue to limit opportunities to address inequities in nutrition to improve the nutritional status of the older population and achieve healthy aging.

Dietary deficiencies are considered to be the main causes of MD, which are intimately linked to food insecurity and poverty.^7,126 Data exploring the link between dietary practices and geriatric syndromes are scarce, and where is does exist, is poorly documented across the region. In addition, national diet and food policies vary across Latin American countries, which may contribute to the prevalence of MD, where known. Fortification of staple foods such as wheat and maize, with critical micronutrients including iron, vitamin A, zinc, calcium, and vitamin D, is a strategy that has been successfully used to address MD at the population level.¹²⁷ However, surveillance in the adherence to fortification guidelines is necessary in counties where fortification is not mandatory. For example, a study in 2018 conducted in Mexico City reported that only a low proportion of flours were adequately fortified, despite national policy recommending fortification.^128,129

Most countries in the region have implemented food fortification programs, such as adding folic acid to wheat and corn flours which explains the decline in the prevalence of FD in the region.⁵¹ What is perhaps missing is research into the effects of supraphysiological levels of some micronutrients, such as folic acid and vitamin A, and their effect on outcomes in OA, some of whom may also be participating in the supplementation programs.

Supplementation strategies have been effective when designed to target specific populations. For example, in Chile the program “Complementary Feeding for older adults” was designed to address VB12 deficiencies in the Chilean OA population. This program supplemented 58% of the daily recommended intake of B12¹³⁰ but previous reports had already shown that this dose would be insufficient.⁴⁷ When safely implemented targeted population strategies are cost-effective approaches to improve micronutrient status, health, and aging-related outcomes.¹³¹

Final Remarks

Micronutrient deficiency is detrimental for health across the whole lifespan. The risk of MD increases with age. A more comprehensive understanding of the main drivers of MD in LAC is needed in order to generate public health-level solutions that improve overall health, independence, and quality of life for OA. The OA population is projected to grow in Latin America which brings challenges to the health system unless early nutritional interventions are delivered to maximize healthy aging. Effective screening of MD will be a critical step to maintain biological function and preserve functionality for at-risk populations. Public health policies focusing on the prevention of malnutrition offer an economic alternative to costly treatment of potentially preventable chronic conditions.

Investment in research and capacity building in the region is crucial to identify equitable solutions to enable healthier populations. By investing in targeted research, we will gain valuable insights into factors contributing to micronutrient deficiencies in OA in LAC. Such insights will inform the development of targeted interventions, policy recommendations, and educational programs aimed at promoting healthy aging and improving the overall well-being of OA. Concurrently, building capacity among health care professionals, policymakers, and community stakeholders will foster a collaborative environment for effective implementation and sustainability of interventions.

Studies that adopt a life-course perspective will enable better understanding of early social determinants, nutritional interventions, long-term outcomes^132,133 and identification of the most cost-effective strategies for the prevention and treatment of age-related diseases associated with MD.

Conclusions

This narrative review describes the reported prevalence of micronutrient deficiencies in OA in Latin America. Only a small number of countries in the region (Brazil, Chile, Ecuador, Costa Rica, and Mexico) have reported any micronutrient data for their populations through representative surveys. These countries are among the highest development index rankings for the region (in the top 10) with minimal Caribbean representation (Tobago). Vitamin D and B12 are the most studied micronutrients in this population, being Vitamin D deficiency reported as the most prevalent. Other micronutrient deficiencies (Vitamin C, E, A, copper, zinc, iron, and selenium) are reported with lower frequency, while others such as magnesium are not reported at all. The limited availability of data, lack of standardized criteria for acceptable micronutrient levels in OA, and the need for biomarker infrastructure in the region, pose significant obstacles to the accurate determination of MD prevalence and to design and implement targeted interventions. Future research and public health efforts should prioritize addressing these challenges to improve the nutritional status and overall health of OA in the Latin American region.

Footnotes

Acknowledgments

The authors thank Alison Canty for critical revision of the manuscript.

Author Contributions

The main author of this work declares that all authors have contributed and work on the development of it as follows. VDG: Conception and design, literature search, analyses, and interpretation of data, writing manuscript. RPG: Literature search, analyses, and interpretation of data, drafting manuscript. ODF: Literature search, analyses, and interpretation of data, drafting manuscript. All authors: Read and agreed to the published version of the manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support for the publication of this article from Fundación Iberoamericana de Nutrición (FINUT). The funders of the publication had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

References

OMS. Envejecimiento y Salud. En: World Health Organization; 2022. Accessed May 2023. https://Www.Who.Int/Es/News-Room/Fact-Sheets/Detail/Ageing-and-Health

Ritchie

The world population is changing: for the first time there are more people over 64 than children younger than 5. OurWorldInData.Org. 2019. https://Ourworldindata.Org/Population-Aged-65-Outnumber-Children.

Economic Commission for Latin America and the Caribbean (ECLAC), Demographic Observatory, 2022(LC/PUB.2022/13-P), Santiago; 2022. www.issuu.com/publicacionescepal/stacks

Turra

Fernandes

. Demographic transition opportunities and challenges to achieve the sustainable development goals in Latin America and the Caribbean. Project Documents. 2020. Accessed May 2023. www.cepal.org/apps

Ruano

Rodríguez

Rossi

Maceira

. Understanding inequities in health and health systems in Latin America and the Caribbean: a thematic series. Int J Equity Health. 2021;20(1):94. doi:10.1186/s12939-021-01426-1

Institute for Health Metrics and Evaluation (IHME). GBD Compare. Seattle, WA: IHME, University of Washington; 2019. Accessed April 23, 2022. http://vizhub.healthdata.org/gbd-compare

Ćurko-Cofek

. Micronutrients in ageing and longevity. In: SIS

Rattan

Kaur

eds. Nutrition, Food and Diet in Ageing and Longevity. Springer; 2021: 63–83. doi:10.1007/978-3-030-83017-5_4

Schmauck-Medina

Molière

Lautrup

, et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging. 2022;14(16):6829–6839. doi:10.18632/aging.204248

O’Connor

Molloy

Laird

Kenny

O’Halloran

. Sustaining an ageing population: the role of micronutrients in frailty and cognitive impairment. Proceedings of the Nutrition Society. 2023:1–14. doi:10.1017/S0029665123002707

10.

UN Decade of Healthy Ageing: 2020. Plan of Action. Accessed June 13, 2023. https://cdn.who.int/media/docs/default-source/decade-of-healthy-ageing/decade-proposal-final-apr2020-en.pdf?sfvrsn=b4b75ebc_28

11.

Galicia

Grajeda

De Romaña

. Nutrition situation in Latin America and the Caribbean: current scenario, past trends, and data gaps. Revista Panamericana de Salud Publica/Pan American Journal of Public Health. 2016;40(2):104–113.

12.

Martinho

Tinôco

ALA

Ribeiro

. Prevalence and factors associated with vitamin B12 deficiency in elderly from Vicosa/MG, Brasil. Nutr Hosp. 2015;32(5):2162–2168.

13.

Olivares

Hertrampf

Capurro

Wegner

. Prevalence of anemia in elderly subjects living at home: role of micronutrient deficiency and inflammation. Eur J Clin Nutr. 2000;54(11):834–839. doi:10.1038/sj.ejcn.1601099

14.

Sánchez

Albala

Herlramp

, et al. [Prevalence of vitamin B-12 deficiency in older adults]. Rev Med Chil. 2010;138(1):44–52. doi:/S0034-98872010000100006

15.

Castillo-Lancellotti

Margozzini

Valdivia

, et al. Nivel sérico de folato y vitamina B12 en adultos mayores chilenos. Resultados de la Encuesta Nacional de Salud ENS 2009-2010. Rev Med Chil. 2013;141(9):1107–1116. doi:10.4067/S0034-98872013000900002

16.

Dinamarca-Montecinos

Vásquez-Leiva

. Are older adults with hip fractures a specific risk group for vitamin B12 deficiency? JCSM Clin Rep. 2022;7(2):44–52. doi:10.1002/crt2.48

17.

Ministerio de Salud de Costa Rica. 2012. Encuesta Nacional de Nutrición 2008-2009. Fasculo 2: Micronutrientes/Ministerio de Salud, Instituto Cstarricense de Investigación y Enseñanza en Nutrición y Salud, Caja Costarricense de Seguro Social, Instituto Costarricense de Estadística y Censos, Instituto Costarricense sobre Drogas. El Ministerio. Accessed May 2023. https://www.binasss.sa.cr/opac-ms/media/digitales/Encuesta%20nacional%20de%20nutrici%C3%B3n.%20Fasc%C3%ADculo%202.%20Micronutrientes.pdf

18.

Hamer

Sempértegui

Estrella

, et al. Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians. J Nutr. 2009;139(1):113–119. doi:10.3945/jn.108.095091

19.

Vinueza Veloz

Carpio Arias

Vargas Mejía

, et al. Cognitive function and vitamin B12 and D among community-dwelling elders: a cross-sectional study. Clin Nutr ESPEN. 2022;50:270–276. doi:10.1016/j.clnesp.2022.05.004

20.

Pereda

Pacheco

Astiazarán-García

Esparza-Romero

Alemán-Mateo

. Vitamina B12 y folato en adultos mayores urbanos no institucionalizado. Arch Latinoam Nutr. 2006;56(2):135–140.

21.

De la Cruz-Góngora

Salinas-Rodríguez

Flores-Aldana

Villalpando

. Etiology of anemia in older Mexican adults: the role of hepcidin, vitamin A and vitamin D. Nutrients. 2021;13(11):3814. doi:10.3390/nu13113814

22.

Diaz

Custodio

Montesinos

, et al. Thyroid dysfunction, vitamin B12, and folic acid deficiencies are not associated with cognitive impairment in older adults in Lima, Peru. Front Public Health. 2021;9:676518. doi:10.3389/fpubh.2021.676518

23.

Hirsch

De la Maza

Barrera

Gattás

Petermann

Bunout

. The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people. J Nutr. 2002;132(2):289–291. doi:10.1093/jn/132.2.289

24.

Meertens

Díaz

Solano

Baron

Rodríguez

. Homocisteína, acido fólico y vitamina B12 en adultos mayores venezolanos. Arch Latinoam Nutr. 2007;57(1):26–32.

25.

Oliveri

Plantalech

Bagur

, et al. High prevalence of vitamins D insufficiency in healthy elderly people living at home in Argentina. Eur J Clin Nutr. 2004;58(2):337–342. doi:10.1038/sj.ejcn.1601786

26.

Saraiva

Cendoroglo

Ramos

Araújo

LMQ

Vieira

JGH

Kunii

. Influence of ultraviolet radiation on the production of 25 hydroxyvitamin D in the elderly population in the city of São Paulo (23° 34’S), Brazil. Osteoporosis Int 2005;16. doi:10.1007/s00198-005-1895-3.

27.

Pereira-Santos

Dos Santos

JYG

Carvalho

Dos Santos

Oliveira

. Epidemiology of vitamin D insufficiency and deficiency in a population in a sunny country: geospatial meta-analysis in Brazil. Crit Rev Food Sci Nutr. 2019;59(13):2102–2109. doi:10.1080/10408398.2018.1437711

28.

Lima-Costa

Mambrini

JVM

de Souza-Junior

PRB

, et al. Nationwide vitamin D status in older Brazilian adults and its determinants: The Brazilian Longitudinal Study of Aging (ELSI). Sci Rep. 2020;10(1):13521. doi:10.1038/s41598-020-70329-y

29.

Carrasco

Domínguez De

Martínez

, et al. Niveles de vitamina D en adultos mayores saludables chilenos y su relación con desempeño funcional. Rev Med Chil. 2014;142(11):1385–1391. doi:10.4067/S0034-98872014001100004

30.

Ministerio de Salud. Informe Encuesta Nacional de Salud 2016-2017: Vitamina D. Ministerio de Salud: Santiago de Chile; 2018. https://goo.gl/oe2iVt

31.

Orces

. Vitamin D status among older adults residing in the littoral and andes mountains in ecuador. Sci World J. 2015;2015. doi:10.1155/2015/545297.

32.

Sud

Montenegro-Bethancourt

Bermúdez

Heaney

Armas

Solomons

. Older Mayan residents of the western highlands of Guatemala lack sufficient levels of vitamin D. Nutr Res. 2010;30(11):739–746. doi:10.1016/j.nutres.2010.10.003

33.

Carrillo-Vega

García-Peña

Gutiérrez-Robledo

Pérez-Zepeda

. Vitamin D deficiency in older adults and its associated factors: a cross-sectional analysis of the Mexican Health and Aging Study. Arch Osteoporos. 2017;12(1):8. doi:10.1007/s11657-016-0297-9

34.

Carrazco-Peña

Farías-Moreno

Del

TEM

, et al. Componentes de fragilidad, sarcopenia y su asociación con insuficiencia de vitamina D. Estudio transversal analítico. Gac Med Mex. 2022;158(6):343–348. doi:10.24875/GMM.M22000711

35.

Mendoza-Garcés

Velázquez-Alva

Cabrer-Rosales

Arrieta-Cruz

Gutiérrez-Juárez

Irigoyen-Camacho

. Vitamin D deficiency is associated with handgrip strength, nutritional status and T2DM in community-dwelling older Mexican women: a cross-sectional study. Nutrients. 2021;13(3):736. doi:10.3390/nu13030736

36.

Suárez-Martínez

Pérez

Cruz

Khorsandi

Chardón

Ferder

. Importance of vitamin D and vitamin D levels status in Puerto Ricans. J Health Care Poor Underserved. 2013;24(4 Suppl):38–47. doi:10.1353/hpu.2014.0000

37.

Miljkovic

Bodnar

Cauley

, et al. Low prevalence of vitamin D deficiency in elderly Afro-Caribbean men. Ethn Dis. 2011;21(1).

38.

Sales

Rogero

Sarti

Fisberg

. Prevalence and factors associated with iron deficiency and anemia among residents of urban areas of São Paulo, Brazil. Nutrients. 2021;13(6):1888. doi:10.3390/nu13061888

39.

Contreras-Manzano

de la Cruz

Villalpando

Rebollar

Shamah-Levy

. Anemia and iron deficiency in Mexican elderly population: results from the Ensanut 2012. Salud Publica Mex. 2015;57(5):394–402.

40.

De la Cruz-Góngora

Rivera-Pasquel

Shamah-Levy

Villalpando-Hernández

. Iron deficiency is not the main contributor to anemia in older Mexican adults: results from the National Health and Nutrition Survey 2018-19. Salud Publica Mex. 2021; 63:412–421. doi:10.21149/12154

41.

González

De la Cruz-Góngora

Rodríguez

. Serum retinol levels are associated with cognitive function among community-dwelling older Mexican adults. Nutr Neurosci. 2021;25(9):1881–1888. doi:10.1080/1028415X.2021.1913315

42.

Marchetti

da Silva

Freiria

, et al. Association between zinc deficiency and cognitive declinin community-dwelling older adults. Cien Saude Colet. 2022;27(7):2805–2816. doi:10.1590/1413-81232022277.19932021EN

43.

Thakkar

Billa

. Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?—Clearing the confusion. Eur J Clin Nutr. 2015;69(1). doi:10.1038/ejcn.2014.165

44.

Stover

. Physiology of folate and vitamin B12 in health and disease. Nutr Rev. 2004;62(6 Pt 2):S3–S12. doi:10.1111/j.1753-4887.2004.tb00070.x

45.

Scott

Baranov

. Chapter 8—Neurologic diseases. In: Fleisher

, ed. Anesthesia and Uncommon Diseases. Sixth Edition. W.B. Saunders; 2012:251–295. doi:https://doi.org/10.1016/B978-1-4377-2787-6.00008-5

46.

Brito

Hertrampf

Olivares

, et al. Folatos y vitamina B12 en la salud humana. Rev Med Chil. 2012;140(11). doi:10.4067/S0034-98872012001100014

47.

Sanchez

Albala

Lera

Dangour

Uauy

. Effectiveness of the National Program of Complementary Feeding for older adults in Chile on vitamin B12 status in older adults; secondary outcome analysis from the CENEX study (ISRCTN48153354). Nutr J. 2013;12(1):124. doi:10.1186/1475-2891-12-124

48.

Castillo-Lancellotti

Margozzini

Valdivia

, et al. Serum folate, Vitamin B12 and cognitive impairment in Chilean older adults. Public Health Nutr. 2015;18(14):2600–2608. doi:10.1017/S1368980014003206

49.

Lanyau-Domínguez

Macías-Matos

De Jesús Llibre-Rodríguez

, et al. Levels of vitamins and homocysteine in older adults with Alzheimer disease or mild cognitive impairment in Cuba. MEDICC Rev. 2020;22(4):40–47. doi:10.37757/MR2020.V22.N4.14

50.

Fedosov

Brito

Miller

Green

Allen

. Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points. Clin Chem Lab Med. 2015;53(8):1215–1225. doi:10.1515/cclm-2014-0818

51.

Brito

Mujica-Coopman

Olivares

Lopez de Romana

Cori

Allen

. Folate and Vitamin B12 status in Latin America and the Caribbean: an update. Food Nutr Bull. 2015;36(2 Suppl):S109–S118. doi:10.1177/0379572115585772

52.

Miller

Garrod

Allen

Haan

Green

. Metabolic evidence of Vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate. Am J Clin Nutr. 2009;90(6):1586–1592. doi:10.3945/ajcn.2009.27514

53.

Brito

Miller

Fedosov

, et al. Low vitamin B12 status and less response to vitamin B12 treatment in Chilean B12-deficient elderly with high serum folate (135.8). FASEB J. 2014;28(S1). doi:10.1096/fasebj.28.1_supplement.135.8

54.

Morris

Selhub

Jacques

. Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study. J Am Geriatr Soc. 2012;60(8):1457–1464. doi:10.1111/j.1532-5415.2012.04076.x

55.

Moore

Ames

Mander

, et al. Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts. J Alzheimer’s Dis. 2014;39(3):661–668. doi:10.3233/JAD-131265

56.

O’Connor

DMA

Laird

Carey

, et al. Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from the Irish Longitudinal Study on Ageing (TILDA). BrJ Nutr. 2020;124(6):602–610. doi:10.1017/S0007114520001427

57.

Doets

Ueland

Tell

, et al. Interactions between plasma concentrations of folate and markers of vitamin B12 status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study. British J Nutr. 2014;111(6):1085–1095. doi:10.1017/S000711451300336X

58.

Freire

Rojas

Pazmiño

, et al. Encuesta Nacional de Salud, Bienestar y Envejecimiento SABE I Ecuador 2009–2010. Aliméntate Ecuador, Universidad San Francisco de Quito; 2010. ISBN: 9789978929087

59.

Venkatesh

Sharma

Ananthan

Subbiah

Durga

. Micronutrient’s deficiency in India: a systematic review and meta-analysis. J Nutr Sci. 2021;10. doi:10.1017/jns.2021.102

60.

Holick

Binkley

Bischoff-Ferrari

, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930. doi:10.1210/jc.2011-0385

61.

Mendes

Gomes

APO

Araújo

Coelho

ASG

Carvalho

KMB

Botelho

. Prevalence of vitamin D deficiency in South America: a systematic review and meta-analysis. Nutr Rev. 2023. doi:10.1093/nutrit/nuad010

62.

Gamarra

. Vitamina D, cognición y demencia; revisión sistemática y metaanálisis: Lectura Crítica DARE. Revista Espanola de Nutricion Humana y Dietetica. 2017;21(4):400–402. doi:10.14306/renhyd.21.4.302

63.

Palacios

González

. La deficiencia de vitamina D es un problema global de salud pública. Anales Venezolanos de Nutricion. 2014;27(1):57–72.

64.

Gallagher

. Vitamin D and aging. Endocrinol Metab Clin North Am. 2013;42(2):319–332. doi:10.1016/J.ECL.2013.02.004

65.

Bocheva

Slominski

. The impact of vitamin D on skin aging. Int J Mol Sci. 2021;22(16):9097. doi:10.3390/ijms22169097

66.

Kandula

Dobre

Schold

Schreiber

Mehrotra

Navaneethan

. Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol. 2011;6(1):50–62. doi:10.2215/CJN.03940510

67.

Pereira-Santos

Costa

PRF

Assis

AMO

Santos

CAST

Santos

. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obe Rev. 2015;16(4):341–349. doi:10.1111/obr.12239

68.

Kim

Song

, et al. The factors associated with vitamin D deficiency in community dwelling elderly in Korea. Nutr Res Pract. 2018;12(5):387–395. doi:10.4162/nrp.2018.12.5.387

69.

Marcos-Pérez

Sánchez-Flores

Proietti

, et al. Low vitamin D levels and frailty status in older adults: a systematic review and meta-analysis. Nutrients. 2020;12(8):1–20. doi:10.3390/nu12082286

70.

Durmus

Kara

, et al. The relationship between vitamin D deficiency and mortality in older adults before and during COVID-19 pandemic. Heart Lung. 2023;117–123.

71.

Murad

Elamin

Abu Elnour

, et al. The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):2997–3006. doi:10.1210/jc.2011-1193

72.

Goodwill

Szoeke

. A systematic review and meta-analysis of the effect of low Vitamin D on cognition. J Am Geriatr Soc. 2017;65(10):2161–2168. doi:10.1111/jgs.15012

73.

Qorbani

Zarei

Moradi

, et al. Effect of vitamin D supplementation on cardiac-metabolic risk factors in elderly: a systematic review and meta-analysis of clinical trials. Diabetol Metab Syndr. 2022;14(1):1–15. doi:10.1186/s13098-022-00859-0

74.

Jayedi

Rashidy-Pour

Shab-Bidar

. Vitamin D status and risk of dementia and Alzheimer’s disease: a meta-analysis of dose-response. Nutr Neurosci. 2019;22(11):750–759. doi:10.1080/1028415X.2018.1436639

75.

van der Schaft

Koek

Dijkstra

Verhaar

HJJ

van der Schouw

Emmelot-Vonk

. The association between vitamin D and cognition: a systematic review. Ageing Res Rev. 2013;12(4):1013–1023. doi:10.1016/j.arr.2013.05.004

76.

Beauchet

Cooper-Brown

Allali

. Vitamin D supplementation and cognition in adults: a systematic review of randomized controlled trials. CNS Drugs. 2021;35(12):1249–1264. doi:10.1007/s40263-021-00876-z

77.

Guzek

Kołota

Lachowicz

Skolmowska

Stachoń

Głąbska

. Effect of Vitamin D supplementation on depression in adults: a systematic review of randomized controlled trials (RCTs). Nutrients. 2023;15(4):951. doi:10.3390/nu15040951

78.

Pereira

Dantas Damascena

Galvão Azevedo

de Almeida Oliveira

da Mota Santana

. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022;62(5):1308–1316. doi:10.1080/10408398.2020.1841090

79.

Tentolouris

Samakidou

Eleftheriadou

Tentolouris

Jude

. The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression. Diabetes Metab Res Rev. 2022;38(4):e3517. doi:10.1002/dmrr.3517

80.

WHO. Iron deficiency anaemia: Assessment, prevention, and control. A guide for programme managers. World Health Organization. 2001:114. doi:10.1136/pgmj.2009.089987

81.

Nairz

Theurl

Wolf

Weiss

. Iron deficiency or anemia of inflammation?: Differential diagnosis and mechanisms of anemia of inflammation. Wien Med Wochenschr. 2016;166(13-14):411–423. doi:10.1007/s10354-016-0505-7

82.

Nemeth

Ganz

. Hepcidin-ferroportin interaction controls systemic iron homeostasis. Int J Mol Sci. 2021;22(12):6493. doi:10.3390/ijms22126493

83.

Weiss

Goodnough

. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–1023. doi:10.1056/NEJMra041809

84.

WHO. WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. World Health Organization; 2020.

85.

Kassebaum

Jasrasaria

Naghavi

, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123(5):615–624. doi:10.1182/blood-2013-06-508325

86.

Romano

Paglia

Bellanti

, et al. Molecular aspects and treatment of iron deficiency in the elderly. Int J Mol Sci. 2020;21(11): 3821. doi:10.3390/ijms21113821

87.

Orces

. Prevalence of anemia among older adults residing in the coastal and Andes mountains in Ecuador: results of the SABE survey. Curr Gerontol Geriatr Res. 2017;2017:4928786. doi:10.1155/2017/4928786

88.

Marín

Rivadulla

Negro

, et al. Population study of the prevalence of anaemia in the adult population of Buenos Aires, Argentina. Aten Primaria. 2008;40(3):133–138. doi:10.1157/13116628

89.

Kassebaum

. The global burden of anemia. Hematol Oncol Clin North Am. 2016;30(2):247–308. doi:10.1016/j.hoc.2015.11.002

90.

Philip

KEJ

Sadaka

Polkey

Hopkinson

Steptoe

Fancourt

. The prevalence and associated mortality of non-anaemic iron deficiency in older adults: a 14 years observational cohort study. Br J Haematol. 2020;189(3):566–572. doi:10.1111/bjh.16409

91.

Guedes

Muenz

Zee

, et al. Serum biomarkers of iron stores are associated with increased risk of all-cause mortality and cardiovascular events in nondialysis CKD patients, with or without anemia. J Am Soc Nephrol. 2021;32(8):2020–2030.

92.

Yan

Xing

Dong

Zhang

. Role of iron-related oxidative stress and mitochondrial dysfunction in cardiovascular diseases. Oxid Med Cell Longev. 2022;2022:512455. doi:10.1155/2022/5124553

93.

Marzetti

Seo

Kim

Prolla

Leeuwenburgh

. The emerging role of iron dyshomeostasis in the mitochondrial decay of aging. Mech Ageing Dev. 2010;131(7-8):487–493. doi:10.1016/j.mad.2010.04.007

94.

Ward

Zucca

Duyn

Crichton

Zecca

. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014;13(10):1045–1060. doi:10.1016/S1474-4422(14)70117-6

95.

Aquino

Bizzi

Grisoli

, et al. Age-related iron deposition in the basal ganglia: Quantitative analysis in healthy subjects. Radiology. 2009;252(1):165–172. doi:10.1148/radiol.2522081399

96.

Altamura

Muckenthaler

. Iron toxicity in diseases of aging: Alzheimer’s disease, Parkinson’s disease and atherosclerosis. J Alzheimer’s Dis. 2009;16(4):879–895. doi:10.3233/JAD-2009-1010

97.

Ndayisaba

Kaindlstorfer

Wenning

. Iron in neurodegeneration—Cause or consequence? Front Neurosci. 2019;13:180. doi:10.3389/fnins.2019.00180

98.

Basuli

Stevens

Torti

. Epidemiological associations between iron and cardiovascular disease and diabetes. Front Pharmacol. 2014;5:117. doi:10.3389/fphar.2014.00117

99.

Kadoglou

NPE

Biddulph

Rafnsson

Trivella

Nihoyannopoulos

Demakakos

. The association of ferritin with cardiovascular and all-cause mortality in community-dwellers: The English Longitudinal Study of Ageing. PLoS One. 2017;12(6):e0178994. doi:10.1371/journal.pone.0178994

100.

Dadon

SBE

Reifen

. Vitamin A and the epigenome. Crit Rev Food Sci Nutr. 2017;57(11):2404–2411. doi:10.1080/10408398.2015.1060940

101.

Michaëlsson

Lithell

Vessby

Melhus

. Serum retinol levels and the risk of fracture. N Engl J Med. 2003;348(4):287–294. doi:10.1056/nejmoa021171

102.

Huang

Liu

Brand

Zheng

. Role of vitamin A in the immune system. J Clin Med. 2018;7(9):258. doi:10.3390/jcm7090258

103.

Gruz-Gibelli

Chessel

Allioux

, et al. The Vitamin A derivative all-trans retinoic acid repairs amyloid-β-induced double-strand breaks in neural cells and in the murine neocortex. Neural Plast. 2016;2016:3707406. doi:10.1155/2016/3707406

104.

Wołoszynowska-Fraser

Kouchmeshky

McCaffery

. Vitamin A and retinoic acid in cognition and cognitive disease. Annu Rev Nutr. 2020;40:247–272. doi:10.1146/annurev-nutr-122319-034227

105.

Lewis

Meydani

. Regulatory role of vitamin E in the immune system and inflammation. IUBMB Life. 2019;71(4):487–494. doi:10.1002/iub.1976

106.

Singh

Devaraj

Jialal

. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr. 2005;25:151–174. doi:10.1146/annurev.nutr.24.012003.132446

107.

Myint

Thein

Tun

Saeed

. Copper deficiency anemia: review article. Ann Hematol. 2018;97(9):1527–1534. doi:10.1007/s00277-018-3407-5

108.

Gać

Czerwińska

Macek

, et al. The importance of selenium and zinc deficiency in cardiovascular disorders. Environ Toxicol Pharmacol. 2021;82:103553. doi:10.1016/j.etap.2020.103553

109.

Vural

Avery

Kalogiros

Coneyworth

Welham

SJM

. Trace mineral intake and deficiencies in older adults living in the community and institutions: a systematic review. Nutrients. 2020;12(4):1072. doi:10.3390/nu12041072

110.

Haase

Mocchegiani

Rink

. Correlation between zinc status and immune function in the elderly. Biogerontology. 2006;7(5-6):421–428. doi:10.1007/s10522-006-9057-3

111.

Barnett

Dao

Hamer

, et al. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial1. Am J Clin Nutr. 2016;103(3):942–951. doi:10.3945/ajcn.115.115188

112.

Meunier

O’Connor

Maiani

, et al. Importance of zinc in the elderly: the ZENITH study. Eur J Clin Nutr. 2005;59(Suppl 2):S1–S4. doi:10.1038/sj.ejcn.1602286

113.

Mocchegiani

Bertoni-Freddari

Marcellini

Malavolta

. Brain, aging and neurodegeneration: role of zinc ion availability. Prog Neurobiol. 2005;75(6):367–390. doi:10.1016/j.pneurobio.2005.04.005

114.

Constantinidis

. The hypothesis of zinc deficiency in the pathogenesis of neurofibrillary tangles. Med Hypotheses. 1991;35(4):319–323. doi:10.1016/0306-9877(91)90277-6

115.

Maguire

Neytchev

Talwar

McMillan

Shiels

. Telomere homeostasis: interplay with magnesium. Int J Mol Sci. 2018;19(1). doi:10.3390/ijms19010157

116.

Barbagallo

Veronese

Dominguez

. Magnesium in aging, health and diseases. Nutrients. 2021;13(2):463. doi:10.3390/nu13020463

117.

Yamanaka

Shindo

Oka

. Magnesium is a key player in neuronal maturation and neuropathology. Int J Mol Sci. 2019;20(14):3439. doi:10.3390/ijms20143439

118.

Rosique-Esteban

Guasch-Ferré

Hernández-Alonso

Salas-Salvadó

. Dietary magnesium and cardiovascular disease: a review with emphasis in epidemiological studies. Nutrients. 2018;10(2):168. doi:10.3390/nu10020168

119.

Durlach

Pagès

Bac

Bara

Guiet-Bara

. Chronopathological forms of asthma due to magnesium depletion with hypo- or hyper-function of the biological clock: therapeutic implications. In: Miller

ed. New Developments in Asthma Research. Nova Science Publishers, Inc.; 2006:1–53.

120.

Veronese

Pizzol

Smith

Dominguez

Barbagallo

. Effect of magnesium supplementation on inflammatory parameters: a meta-analysis of randomized controlled trials. Nutrients. 2022;14(3):679. doi:10.3390/nu14030679

121.

Peeri

Egan

Chai

Tao

. Association of magnesium intake and vitamin D status with cognitive function in older adults: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014. Eur J Nutr. 2021;60(1):465–474. doi:10.1007/s00394-020-02267-4

122.

Cherbuin

Kumar

Sachdev

Anstey

. Dietary mineral intake and risk of mild cognitive impairment: The PATH through life project. Front Aging Neurosci. 2014;6(FEB):4. doi:10.3389/fnagi.2014.00004

123.

Ozawa

Ninomiya

Ohara

, et al. Self-reported dietary intake of potassium, calcium, and magnesium and risk of dementia in the Japanese: the Hisayama Study. J Am Geriatr Soc. 2012;60(8):1515–1520. doi:10.1111/j.1532-5415.2012.04061.x

124.

Wong

. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015;21(2):155–164. doi:10.12809/hkmj144383

125.

Lowe

. The global challenge of hidden hunger: perspectives from the field. Proc Nutr Soc. 2021;80(3):283–289. doi:10.1017/S0029665121000902

126.

Siddiqui

Salam

Lassi

Das

. The intertwined relationship between malnutrition and poverty. Front Public Health. 2020;8:453. doi:10.3389/fpubh.2020.00453

127.

Allen

De Benoist

Dary

Hurrell

. WHO/FAO Guidelines on Food Fortification with Micronutrients. Geneva: WHO. 2006.

128.

Changing Markets Foundation. ¡Al Grano!: ¿qué Marcas de Harinas Incumplen Con La Normativa de Fortificación Mexicana?; 2019. Accessed June 5, 2023. http://changingmarkets.org/wp-content/uploads/2019/02/Al-Grano-Spanish-web-double-page.pdf

129.

Orjuela

Mejia-Rodriguez

Quezada

, et al. Fortification of bakery and corn masa-based foods in Mexico and dietary intake of folic acid and folate in Mexican National Survey Data. Am J Clin Nutr. 2019;110(6):1434–1448. doi:10.1093/ajcn/nqz224

130.

Sánchez

Albala

Hertrampf

, et al.

Déficit de vitamina B-12 en adultos mayores: ¿un problema de salud pública en Chile?

Rev Med Chil. 2010;138(1):44–52. doi:10.4067/s0034-98872010000100006

131.

World Health Organization. Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification. 2023. Accessed June 5, 2023. https://apps.who.int/gb/ebwha/pdf_files/EB152/B152_CONF5-en.pdf

132.

Jones

Gilman

Cheng

Drury

Hill

Geronimus

. Life course approaches to the causes of health disparities. Am J Public Health. 2019;109(S1):S48–S55. doi:10.2105/AJPH.2018.304738

133.

Kuh

Sayer

Ben

Shlomo Y

, et al. A life course approach to healthy aging, frailty, and capability. J Geronto A Biol Sci Med Sci. 2007;62(7):717–721. doi:10.1093/gerona/62.7.717

Micronutrient Deficiencies in Older Adults in Latin America: A Narrative Review

Abstract

Background:

Aim:

Methods:

Results:

Conclusion:

Plain language title

Plain language summary

Keywords

Introduction

Methods

Results and Discussion

Commonly Measured Micronutrient Biomarkers

Vitamin B12 and Folate Deficiency

Vitamin D Deficiency

Iron Deficiency

Vitamin A Deficiency

Copper, Zinc, Vitamin E, Vitamin C Selenium, and Magnesium Deficiencies

The Gaps and Challenges

Final Remarks

Conclusions

Footnotes

Acknowledgments

Author Contributions

Declaration of Conflicting Interests

Funding

References