Detrimental impact of solar and geomagnetic activity on plasma B-complex vitamins in the VA normative aging study cohort

Abstract

It has been hypothesized that ultraviolet (UV) radiation can lead to depletion of plasma folate and B₁₂ vitamin, but few studies have investigated effects of other parameters of solar and geomagnetic activity (SGA). We investigated the association between four SGA parameters—interplanetary magnetic field (IMF), sunspot number (SSN), K_p index, and ground shortwave solar radiation (SWR)—and three plasma B-complex vitamins—folate, B₆, and B₁₂—in 910 participants from the Normative Aging Study (NAS) between 1998 and 2017. Mixed-effects regression models were used for 1- to 28-moving day averages of SGA exposure, adjusted for covariates. We compared the impact of SGA in individuals under higher and lower B-complex supplementation (> or < 50th quartile). Our findings show that increases in solar activity variables IMF and SSN were found to be significantly associated with decreases in B₁₂ vitamin. IMF and SSN were associated with decrease in folate levels, especially in individuals under higher levels of B-complex supplementation. No associations were found for SWR and K_p index. To our knowledge, this is the first study that demonstrated the detrimental impact of solar activity on plasma B₁₂ and folate in a large cohort. These findings have clinical implications during periods of high solar activity.

Introduction

Solar activity oscillates over ~ 11-year cycles, in which activity levels rise and fall, affecting life on Earth¹. Directly, the broad range of solar electromagnetic radiation—including visible light, ultraviolet (UV) light, infrared, radio waves, X-rays, and gamma rays—can modulate the circadian rhythm in humans and other organisms². Indirectly, solar activity modulate short-term fluctuations in the Earth’s magnetic field, called geomagnetic disturbances (GMDs), which influence human physiology and standard metabolism, enhancing the risk of mortality^3,4 and morbidity such as hypertension^5,6 and cardiovascular diseases (CVD)^3,7. Studies have reported the association between solar UV-radiation and reduced folate^8,9 and B₁₂ vitamin¹⁰, which is linked to several adverse health outcomes.

B-complex vitamins, i.e., folate, B₆, and B₁₂ vitamins, are an important group of micronutrients in the human body, essential for normal growth, development, and physiological function. In the human body, B-complex vitamins play an important role in mediating DNA methylation, and breaking down homocysteine, an amino acid that leads to increased metabolic risk if present in high concentrations. B-complex vitamin deficiency has long been studied as a risk factor for CVD^11–13, cognitive impairment^14,15, adverse birth outcomes^16,17, osteopenia^18,19, skeletal muscle malfunction^20,21, and birth defects²². B-complex vitamin deficiency can also cause megaloblastic anemia²³, affect lipid profile, and induce cholesterol synthesis²⁴. In vitro^25–28 and in vivo^8–10 studies have reported folate and B₁₂ depletion as a result of exposure to UV radiation, and one study has shown solar activity parameter sunspot number (SSN) to potentially modify the relationship between folate deficiency and neonatal developmental disorders²⁹. Nevertheless, there have been no studies that investigated the role of solar activity, beyond UV radiation, and GMD on the risk factor for B-complex vitamin depletion in adult population.

To provide insight into this research gap, the aim of this study is to investigate the impact of solar and geomagnetic activity (SGA) on the levels of plasma folate, B₆, and B₁₂ vitamins in a cohort of healthy elderly men in the Greater Boston, MA region. We also assessed the impact of short-wave solar radiation (SWR) and levels of B-complex supplementation. To our knowledge, this is the first longitudinal cohort study aiming to assess the association of SGA and plasma B-complex vitamin levels.

Results

Descriptive statistics

All subjects were male, and at baseline, had a mean age of 71.62 ± 7.09 years, mean BMI of 28.20 ± 4.02 kg/m², and mean eGFR of 73.05 ± 15.67 ml/min/1.73 m² at the first visit. Most of the cohort is white (97.50%) (Table 1). Approximately, thirteen percent of participants had physician-diagnosed diabetes, and almost twenty percent used to have two or more alcoholic drinks per day. In the first visit, regarding smoking status, 64.30% of subjects were former smokers, 30.40% were never smokers, 5.10% were current smokers; the mean pack-years of the population was 21.97 ± 26.76 pack-years. Plasma levels of folate, B₆, and B₁₂ vitamin in our population presented high variability in the first visit, with mean values of 16.27 ± 12.87 ng/ml, 100.68 ± 97.06 nmol/l, and 494.46 ± 241.70 pg/ml, respectively (Table 1).

Table 1.

Characteristics of the NAS cohort from 1998 to 2017 at baseline and over all follow-up visits.

	First visit	Overall
n	910	3019
Age (mean (SD))	71.62 (7.09)	75.55 (7.36)
Race (%)
Non-white	22 (2.40)	86 (2.80)
White	887 (97.50)	2932 (97.10)
BMI (mean (SD))	28.20 (4.02)	27.97 (4.07)
Diabetes mellitus (n (%))	118 (13.00)	474 (15.70)
Glomerular Filtration Rate—eGFR (mean (SD))	73.05 (15.67)	66.91 (16.13)
Smoking habits (%)
Never	277 (30.40)	948 (31.40)
Current	46 (5.10)	127 (4.20)
Former	585 (64.30)	1939 (64.20)
Package of cigarettes in years (mean (SD))	21.97 (26.76)	19.95 (24.11)
Alcohol consumption n (%))	178 (19.60)	556 (18.40)
Plasma levels
Folate ng/ml—(mean (SD))	16.27 (12.87)	18.18 (16.17)
Vitamin 6—nmol/ml (mean (SD))	100.68 (97.06)	109.44 (108.52)
Vitamin 12—pg/ml (mean (SD))	494.46 (241.70)	533.93 (306.87)
Supplement taking
Folate mcg/day (mean (SD))	537.40 (321.81)	643.3 (361.70)
B6 mg (mean (SD))	12.91 (33.58)	12.61 (31.62)
B12 mcg (mean (SD))	17.74 (23.19)	18.50 (23.87)

Summary statistics of meteorological conditions and SGA variables on the day of visit are displayed in Table 2. Over the study period, the average outdoor temperature during a visit was 13.36 ± 8.86 °C and the average relative humidity was 67.29 ± 17.59%.

Table 2.

Meteorological and space weather conditions on the day of plasma B-complex vitamins measurement in NAS cohort from 1998 to 2017.

Space-weather parameters	n	Mean (SD)	Median	25th	75th
Sunspot number (SSN)	3019	73.35 (67.62)	55	16.50	114
Kp index	3019	18.56 (12.14)	16.04	9.04	25.46
Interplanetary magnetic field (IMF)	3019	5.76 (2.85)	5.20	1.82	6.84
Short-wave solar radiation (SWR)	3019	313.32 (120.45)	322.24	42.56	410.94
Meteorological conditions
Temperature	3019	13.36 (8.86)	13.94	− 14.50	20.44
Relative humidity	3019	67.04 (18.3)	68.05	6.66	81.38

Association between SGA and plasma B-complex vitamins

Overall, we found a negative association of solar activity variables IMF and SSN with B₁₂ vitamin (Fig. 1). There were no significant associations between SWR and K_p Index to B-complex vitamins (Fig. 1) for most exposure windows. The effect estimates of IMF on B₁₂ vitamin were generally stronger for longer exposure windows, with significant negative associations. For example, an IQR of 3.1 nT of IMF for a 20 days moving average prior to the sample collection was associated with − 94.8 pg/ml (95% CI − 135.9, − 53.7; p-value: 7.2E−06) in plasma B₁₂ vitamin levels, while, in the same moving average, an IQR of 130.6 SSN was associated with -71.8 pg/ml (95% CI − 103.4; − 40.1; p-value: 1.00E−05) in B₁₂. Although for folate we observed a negative trend with IMF and SSN, the associations were not significant. For IMF, we observed significant negative effects on vitamin B₁₂ in all exposure windows. Whereas the impact of SSN on B₁₂ was similar across all exposure windows, SSN was not associated with folate or B₆ levels in the primary analysis. The results were similar when we adjusted the models for solar radiation (SWR) (supplementary material).

Figure 1.

Effects of SGA on plasma folate, B₆, and B₁₂ vitamins in NAS cohort from 1998 – 2017.

In the secondary analysis, the impact of solar activity was strongly associated in individuals under higher levels of B-complex supplementation (> 50th quartile), while for most subjects with lower supplementation the associations were not meaningful (Fig. 2). In these subjects, IMF and SSN were significantly associated with reduced B₁₂, and only SSN with reduced folate for the most moving day averages (Fig. 2 and supplementary material). For example, an IQR of 3.1 nT IMF was associated with a − 116.7 pg/ml (− 221.1, − 10.9; p-value < 0.000001) in B₁₂, and an IQR of 117.3 SSN was associated with − 97 pg/ml (− 174.8, − 19.2; p-value < 0.000001) for the period of 20 days moving average prior the sample collection. For the same moving day average, and IQR of 112.9 SSN was associated with − 2.7 ng/ml (− 4.9, − 0.6; p-value: 0.0285) in folate (Fig. 2 and supplementary material). IMF was associated with increased B₆ levels in some moving day averages (Fig. 2 and supplementary material). The results were similar when the models were adjusted for SWR. There was a significant association between SWR and reduced B₆ in individuals with higher levels of B₆ [− 156.5 nmol/l (− 298.6; − 14.4; p-value: 0.03)] over the 22-moving day average period.

Figure 2.

Effects of SGA on plasma folate, B₆, and B₁₂ vitamins in NAS cohort from 1998 – 2017 under higher versus lower B-complex supplementation (> or < 50th quartile of B-complex supplementation).

In the IPW analyses, the associations between SGA and B-complex were stronger than in the primary models, which validate our findings (supplementary material).

Discussion

To the best of our knowledge, this is the first study to demonstrate associations between solar activity and B-complex in a large cohort study. Increases in solar activity were found to be significantly associated with decreases in plasma B₁₂ vitamin and folate, but not with depletion of B₆ vitamin, among elderly men enrolled in the VA NAS study. There were no significant associations between SWR or the geomagnetic activity (K_p Index) and any of the B-complex vitamins. The associations with IMF and SSN were similar when the models were adjusted for SWR. Subjects with higher supplementation of B-complex seems to be more susceptible to detrimental impact of solar activity. We hypothesize that increased levels of B-complex vitamins, especially from supplements, may increase the photosensitivity and photodegradation of these vitamins under solar activity-related electromagnetic radiation exposures.

The biological mechanisms through which solar activity can affect plasma B-complex vitamin levels have not yet been investigated. While we found no meaningful associations between B₁₂ and folate and SWR and geomagnetic activity (Kp index), SSN was significantly associated with reduced folate and reduced B₆ was associated with SWR in subjects under higher folate supplementation. Although there is a significant association between SWR exposures and reduced B_6, the effects of UV radiation on B₆ and B₁₂ vitamins are not yet well understood. Most previous studies investigated the effects of UV-radiation on plasma B-vitamins focused on the detrimental impact of UV radiation on plasma folate. In vitro studies have shown folate in blood and skin can be directly degraded when exposed to UV radiation^25–28. More recent studies have shown that folate can also be indirectly degraded by UV radiation through the generation of reactive oxygen species (ROS) that can oxidize 5-Methyltetrahydrofolate (5MTHF), the main active form of folate found in blood³⁰. Valencia-Vera et al. studied seasonal folate degradation associated with UV radiation in a cohort in Spain and found that the risk of folate deficiency was 1.37 times (95% CI 1.29–1.46) greater in summer than in winter, with a correlation to increase in global UV daily dose in study location⁸. Borrandale et al. studied a cohort of childbearing age women and found that, over a 7-day period, women with higher personal exposure to UV radiation had significant decreases in plasma folate, reducing the effectiveness of folate supplementation⁹. Cabrera et al. studied plasma B₁₂ vitamin levels in a cohort of elderly Chileans and found significant negative associations for geographical latitude and solar radiation¹⁰. Skjærvø et al. investigated the effects of solar activity on infant survival using individual-based demographic data in Norway from 1676 to 1878 and found that the average lifespan of individuals born in solar maximum years (i.e., years of high solar activity determined using SSN) was 5.2 years shorter than those born in solar minimum years after controlling for socioeconomic status and ecology, hypothesized to be due to degradation of folate during pregnancy³¹. Lucock et al. studied a cohort of 379 neonates in the UK and reported that SSN predicted two folate-sensitive, epigenomic-related genotypes during the first trimester of pregnancy, shedding light on the effect modification mechanism of solar activity and seasonality on folate-related developmental disorders²⁹. Reduced levels of B₁₂ vitamin or folate affect the production of red blood cells that can evolve to anemia and to detrimental impact on the nervous system health. In periods of intense solar activity, solar ionizing radiation such as UVB and UVC, X-rays, gamma and solar energetic particles are emitted from the Sun, reaching the Earth systems, modifying the homeostasis of the living beings which may include detrimental B₁₂ and folate oscillations. There are indications that higher levels of B-complex increase the individual sensitivity to light exposures, however, further experimental studies are necessary to explain the physiological mechanisms related to the increased susceptibility of individuals with higher levels of B-complex supplementation to detrimental impact of solar activity-related electromagnetic radiation and vice-versa.

In addition, recent studies have shown that the general population has similar adverse health symptoms related to solar activity oscillations to those observed in astronauts, although less acute and intense. Similarly, B-complex deficiencies have been observed in astronauts³². The adverse impact of space weather radiation exposures on B-complex levels in astronauts is also linked to a decrease in mitogen proliferation that reduces immune-inflammatory cells such as Peripheral Blood Mononuclear Cells (PBMCs) and lymphocytes (type of white blood cells), and thus weakens the immunological system^33,34. Interestingly, Tracy et al.³⁵ attributed the solar activity-related decreased white blood cells to the disruption of the circadian rhythm and autonomic nervous system dysregulation in the same elderly cohort of our study³⁵. Indeed, studies have suggested a link between B₁₂ vitamin levels, the 24 h circadian rhythm modulation, and melatonin levels. When there is B₁₂ vitamin deficiency, there is a prolonged phagocytized lamellar structure in the retinal pigment epithelium (RPE) that is also under circadian clock control and melatonin regulation^34,36. Melatonin is a potent nocturnal antioxidant that can protect human RPE via reducing oxidative stress³⁶, possibly mitigating the adverse effects of the dysregulation of the circadian rhythm. Solar activity- related B₁₂ deficiency, reduced melatonin levels, and circadian rhythm disruption may have bidirectional relationships. Consequently, these mechanisms should be further investigated.

Our study has several limitations. It is uncertain whether dietary B vitamin supplementation was adequately assessed for our study, since dietary information was only self-reported from participants. Moreover, our study focused on the short to medium exposure windows for SGA. For B₁₂, effects of IMF and SSN were still strong at day 28 of exposure, and future assessments may focus on longer-term effects of solar activity. Lastly, our study population was predominantly white and elderly men (97.5%) living in Boston area, which makes our results not generalizable to women and populations with a more diverse racial/ethnic demographics. Moreover, the impact of SGA may have gender and age differences. It is important for future studies to include populations more vulnerable to decreases in plasma B-complex vitamins, particularly pregnant women. Nevertheless, our study has many strengths. This is the first longitudinal cohort study to investigate the effects of SGA on plasma B-complex vitamins in elderly men. The investigation of three different SGA variables, rather than just UV radiation or SSN, provides a more comprehensive understanding of how solar activity can affect plasma B-complex vitamins. The study period ranging from 1998 to 2017 coincided with a period of solar cycle 22 and 23³⁷.

Conclusions

We found that increases in solar activity were significantly associated with decreases in B₁₂ vitamin and folate, but not with B₆ vitamin among elderly men enrolled in the VA NAS study. These findings shed light on the current research gap, implying a more complex effect of solar activity on serum B-complex vitamins beyond effects due to ultraviolet radiation. We show that even short oscillations in solar activity can decrease plasma B-complex vitamins despite supplementation. Our study also has important clinical implications, especially in terms of optimal levels of B₁₂ and folate supplementation for vulnerable populations such as elderly populations during years of intense solar activity. Still, further research is needed to better understand the magnitude of B-complex vitamin depletion due to long-term exposure to solar activity and the biological pathways.

Materials and methods

Study population

The study population consisted of men enrolled in the Normative Aging Study (NAS), a cohort established in 1963 by the U.S. Department of Veterans Affairs to study the effects of aging³⁸. NAS recruited men from the Greater Boston Area and all participants were free of chronic diseases at baseline and underwent routine examinations every 3–5 years consisting of physical evaluations, laboratory tests, and standardized questionnaires to collect information on social status, medical history, smoking history, alcohol consumption, food intake and other factors that can influence health. From 1998 to 2017, plasma folate, B₆, and B₁₂ were measured for the NAS cohort. The final sample size for analysis comprised of 910 participants, and 910 with 3019 clinical visits. Each subject had between 1 and 8 visits. The study was approved by the Institutional Review Boards of the Harvard T.H. Chan School of Public Health and the Department of Veterans Affairs. All subjects signed the informed consent to participate in this research.

Plasma folate, B₆, and B₁₂ and dietary intake

Fasting plasma samples were collected at the Veterans Administration field site, stored at -80˚C, and subsequently measured at the U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University. Plasma folate and B₁₂ vitamin were measured by radio assay using a commercial kit from Bio-Rad (Hercules, CA). B₆ vitamin as pyridoxal-5′-phosphate, was measured with an enzymatic method using tyrosine decarboxylase. The Coefficients of Variation (CVs) for assays used were 4.3% for folate, 4.7% for B₁₂ vitamin, and 4.0% for B₆ vitamin.

Dietary intake of B-vitamins was assessed through a version of the Willet semiquantitative Food Frequency Questionnaire, mailed to NAS participants before their examination visit, and analyzed using a nutrient database at the Channing Laboratory of Brigham and Women’s Hospital to obtain estimates of daily vitamin intake. More details can be found elsewhere^15,39.

Weather parameters

The 24-h average ambient temperature (°C) and relative humidity data were obtained from the National Climatic Data Center at the National Oceanic Atmospheric Administration (NOAA)⁴⁰.

Solar and geomagnetic activity assessment

To assess SGA exposures, four proxy variables were used: Interplanetary Magnetic Field (IMF) intensity, Sunspot Number (SSN), Short Wavelength Radiation (SWR), and K_p Index. IMF is part of the solar magnetic field that is carried into interplanetary space by the solar wind, it represents the intensity of the solar magnetic field and is a component of solar activity. SSN is an indicator that measures the quantity of spots on the surface of the Sun that rises and falls during the 11-year solar cycle and is another component of solar activity¹. Ground SWR includes solar visible light (400–780 nm), UVA (315–400 nm), UVB (280–315 nm), and UVC (100–280 nm), representing environmental electromagnetic radiation produced by solar activity. K_p Index is an indicator that characterizes the magnitude of geomagnetic disturbances caused by solar wind. While IMF, SSN, and SWR are parameters for solar activity, K_p Index is a parameter for geomagnetic activity. Together, these four variables depict the interactions between the Sun and the Earth, which potentially have impacts on human health.

The data on IMF, SSN, and K_p Index were obtained from NASA Goddard Space Flight Center’s OMNIWeb website⁴¹. Data on SWR [including visible light, near-ultraviolet (UV), and near-infrared (NIR) spectra] at 1-km grid-level were obtained from NASA’s Daymet database, which uses a collection of algorithms to interpolate and extrapolate daily meteorological data⁴². Total IMF intensity data, expressed in nanotesla (nT), measures the combined IMF strength in all directions and were collected using direct measurement in numerous spacecraft. SSN is measured as the number of dark areas on the Sun’s surface, with diameters ranging from 3500 to 6000 km. SWR is a modeled data obtained from measurements of solar radiation in Watts/m² at ground level during daylight periods, defined as the time of day in seconds when the Sun is above a hypothetical flat horizon. K_p Index quantifies geomagnetic activity and is measured on a 0 to 9 scale (*10), where 0 represents very little activity and 9 represents extreme geomagnetic storms.

To quantify short and medium-term exposure effects, moving averages for day 0 (day of the visit) through day 28 before the visit were calculated for IMF, SSN, K_p Index, and SWR. This was done to study the potential lag between the solar event occurrence and the exposure effects, combined with the lag between exposure and response effects. The exposure window was limited to 28 moving day averages (day of blood collection -day zero- to 28 days prior to the sample collections) to avoid potential confounding by seasonal changes in SGA exposures. Moving day averages are calculated by averaging the exposure parameter over a specific period to establish exposure–response relationships.

Statistical analysis

A mixed-effects linear model with a random intercept for each study subject was used to estimate the impact of SGA parameters on plasma B-complex vitamins. The random intercept for each subject accounted for the longitudinal correlation of measurements of each subject at different visits. The general equation for the model is:

$$Y_{\mathit{ij}}={\beta }_0+{\beta }_1{E}_{\mathit{ij}}+{\beta }_2{X}_{1ij}+\cdots +{\beta }_k{X}_{\mathit{kij}}+b_i+{\epsilon }_{\mathit{ij}}$$

For subject i at visit j, $Y_{\mathit{ij}}$ is the outcome of interest (plasma folate, B₆ or B₁₂ vitamin), $E_{\mathit{ij}}$ is the exposure of interest (1- to 28-day moving average of IMF, SSN, SWR, or Kp Index), $X_{1ij}$ to $X_{\mathit{kij}}$ are covariates of interest, $b_i$ is the subject-specific random intercept that allows for correlation of measurements between different visits.

All models were adjusted for 24-h average ambient temperature, relative humidity, and seasonality, represented as follows:

$$sin\left(2\times \pi \times \frac{dayofyear}{365}\right),cos\left(2\times \pi \times \frac{dayofyear}{365}\right)$$

Additionally, the primary model included the following individual predictors: age at the time of visit (continuous), race (white/black), BMI (continuous), estimated glomerular filtration rate (eGFR) (continuous) based on the chronic kidney disease epidemiology collaboration equation (CKD-EPI 2009)⁴³, dietary B vitamin supplementation (continuous), diabetes mellitus (yes/no), smoking history (current/former/never), pack-years of cigarette smoking (continuous), two or more alcoholic drinks per day (yes/no). We additionally adjusted the models for SWR to check if the impact of SGA was related to the SWR spectra (which represent spectra from infrared to ultraviolet).

In our secondary analysis, we analyzed the impact of SGA on quartiles of B complex supplement (individuals under higher 50th versus lower 50th levels of B-complex supplementation). We established for B₆ supplement cutoff as > or < 50th = 3.7 mg; B₁₂ supplement as > or < 50th =11.3 mg; and folate as > or < 50th = 611.8 mcg. These models were not adjusted for B-complex supplementation.

Furthermore, we applied the inverse probability weights (IPW) to analyze the impact of potential bias as healthier men are more likely to return for follow-up visits⁴⁴. The estimates of the association of SGA with plasma B-complex vitamins were reported for an interquartile range (IQR) increase in exposure, where IQR was calculated as the difference between the 25th and 75th quantiles of the exposure measured. This was done to enable a comparison of the effect sizes of SGA and air pollution variables.

Ethical approval

All methods were carried out in accordance with relevant guidelines and regulations.

Abbreviations

BMI

Body mass index

B₆

B₆ vitamin

B₁₂

B₁₂ vitamin

CI

Confidence intervals

GMD

Geomagnetic disturbance

IMF

Interplanetary magnetic field

IQR

Interquartile range

K_p Index

Planetary K index

NAS

Normative ageing study

SD

Standard deviation

SGA

Solar and geomagnetic activity

SSN

Sunspot number

SWR

Short wave solar radiation (infrared, visible light, UV radiation)

UV

Ultraviolet

Author contributions

P.K. and C.L.Z.V. were involved in conceptualization, developing methodology and supervision. C.L.Z.V. and C.S.L. conducted the formal analysis, visualization and wrote the original draft. A.R., Y.W. and V.W. provided software related assistance. All authors edited and approved the final version of the manuscript.

Data availability

All data generated or analyzed during this study are included in this published article [and its supplementary information files]. The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-024-56916-3.