Multivitamin use ‘a major determinant’ of higher B-vitamin status

By Will Chu

- Last updated on GMT

irculating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use.©iStock
irculating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use.©iStock

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Varying levels of multivitamin supplement use worldwide has new implications for chronic disease risk, circulating biomarker concentrations and nutritional status of regions or populations.

The Nordic study found multivitamin-supplement use highest in the United States, followed by the Nordic region, Australia, and finally the Asian region.

While B vitamins and lipid soluble vitamins were low in Asians, researchers found circulating concentrations of metabolites, inversely related to B vitamins involved in the one-carbon and kynurenine pathways, were high in Asians.

“Through the quantification of circulating concentrations of 7 vitamins and 5 functional B-vitamin markers, we show that B-vitamin status was higher in the US than in the Nordic region, Asia, and Australia, whereas vitamin status, in general, was low in the Asians,”​ the study said.

“The high prevalence of multivitamin-supplement use is suggested to be a major determinant of the higher B-vitamin status in the US.

The one-carbon metabolism (1CM) is a metabolic network that relies on folate and methionine to maintain genome stability and function.

Likewise, the Kynurenine pathway is central to metabolic function. Its disruption is associated with certain genetic disorders.

Food fortification

The study joins a handful of others that have investigated vitamin status as reflected by assessing circulating biomarkers in different regions located across the world.

Circulating concentrations of vitamins and associated metabolites vary due to factors such as diet, lifestyle, vitamin-enrichment and food-fortification practices, and supplement use.

In some countries, food fortification with various vitamins has been implemented to correct identified deficiencies or to reduce disease risk.

In Switzerland, about 250 food products are voluntarily fortified with folic acid, as a measure designed to address neural tube defects.

The UK favours mandatory fortification as flour is enriched with nutrients such as iron, calcium carbonate and thiamin (vitamin B1).

Recent European analyses demonstrated inverse relations between circulating vitamin B-6 [pyridoxal 5′-phosphate (PLP)] and methionine and lung cancer risk​.

In the current investigation, researchers from the University of Bergen, Norway; the International Agency for Research on Cancer in France and Imperial College London in the UK, describe circulating concentrations of 38 biomarkers that are related to vitamin status.

The circulating vitamins looked at include riboflavin, pyridoxal 5′-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol.

In total, 5314 healthy control subjects from the United States, Nordic region, Asia, and Australia took part.

Blood samples were taken between 1974 and 2010 as was smoking status and multivitamin supplement use.

Blood vitamin levels were measured using mass spectrometry and microbiological methods were specifically used to measure the levels of folate and B-12.

Vitamin levels

The team found multivitamin-supplement use was 36.8% in the United States, 26.8% in the Nordic region 6.9% in Asians, and 13.3% in Australians.

Of subjects in which multivitamin use data was available, 27.2% reported the use of such supplements, whereas 72.8% reported no use of such supplements.

The prevalence of multivitamin-supplement use was 36.8% in the United States, 26.8% in the Nordic region (data available for only 205 participants), 6.9% in Asians, and 13.3% in Australians.

Across regions, the spread (CV) of biomarker concentration was largest for folate (39%) and γ-tocopherol (38%), whereas the CV was less than 10% for 17 of 38 biomarkers.

Folate was highest in the US compared with in the other regions. Functional B-vitamin markers (tHcy, MMA, cystathionine, HK, and HK:XA) were generally high in the Asian region and low in the US region, and fat-soluble vitamins A, 25(OH)D, and α-tocopherol were higher in Nordic and Australian regions than in US and Asian regions.

Methionine and downstream OCM biomarkers were generally highest in the Asian region, whereas tryptophan and kynurenines were generally lowest in the US and highest in Asia.

“The B-Vitamin score (BVS) was higher in the US than in the other regions,”​ the study stated.

“The consumption of fortified foods strongly affects B-vitamin status with ready-to-eat cereals being a major source of many vitamins.”

“Within the Nordic region, Norway and Sweden, fortification was limited to only vitamins A and D in dairy products, and the consumption of cod-liver oil provided a further source of vitamin D in Norway, whereas there was no fortification in Finland.”

Asian explanations

The study also explained that in Asia, China had no vitamin fortification during the sampling period, whereas Singapore started fortification with folic acid in 1998, and in Australia, only the fortification of cereals with retinol took place.

Additionally, low circulating vitamin D in Asians was suggested to be related to skin pigmentation and the cultural avoidance of sun exposure.

In trying to explain B-vitamin status and its relation to one-carbon and tryptophan metabolites, the team referred to concentrations of tryptophan metabolite 3-hydroxykynurenine (HK), a B-vitamin marker, and the HK:XA Xanthurenic acid ratio as reliable indicators of vitamin B-6 status.

In the current study, both markers were found to be inversely related to PLP across cohorts.

"The HK:XA ratio has been suggested to be a better functional vitamin B-6 marker than HK alone, but the HK:XA was not the lowest in the United States, which was the population that showed the highest PLP concentrations,"​ the study concluded.

"Kynurenines other than HK were also related, although more weakly than HK was, to circulating concentrations of riboflavin and PLP in a Norwegian population and also across cohorts in this study.

"However, we did not consistently find the anticipated relations across regions. Conceivably, as with total homocysteine (tHcy), additional factors may influence circulating concentrations of tryptophan metabolites."

Source: American Journal of Clinical Nutrition

Published online ahead of print: doi: 10.3945/​ajcn.116.151241

“Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.”

Authors: Øivind Midttun et al.


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