calcium and hair loss
calcium and hair loss

COULD CALCIUM LEVELS BE LINKED TO HAIR LOSS?

Calcium is essential for all living cells and plays a pivotal role in signal pathways and the maintenance of cell function.  Calcium is involved in the building up and the breaking down of metabolic products as well as the synthesis of hormones and membrane dependant processes.  Calcium is also responsible for the transmission of information within a cell, cell development and cell growth.

Calcium deficiency leads to conditions such as osteoporosis, but changes to cell functions can occur even before we reach a clinically deficient state.  Lower than optimal levels of calcium result in weak nails, thin skin and slower hair growth.  Calcium has been shown to have a significant impact on the functional capabilities and growth of the keratin cells that make up the hair fibre and skin [1].  In the absence of a calcium deficiency, could your calcium levels be linked to your hair loss problems?

calcium and hair loss

Calcium is essential for hair growth. Calcium is required for many vital functions in keratin cells.

CALCIUM AND ITS DIRECT LINK TO HAIR GROWTH

Hair growth is dependant on a keratin cell being able to grow and develop (differentiate) into a mature keratin cell. Whether keratin cells grow to its full potential or stalls in early sates depends on local factors.  These factors include local inflammation, nutritional status (such as iron and zinc availability) and other environmental or biological contributions.

Whilst there are a number of reasons why hair may grow slowly or shed excessively, it is clear whether or not calcium plays a direct role in hair loss.  To assess the role of calcium, in hair loss a multi-omics study attempted to shed light on the link between calcium and the function if keratin cells in the hair fibre.

WHAT IS A MUTLI-OMICS STUDY?

Multi-omics is a systems biology approach that analyse molecular components using and computational analysis to find obscure pathways that can offer valuable insights.  In the case of hair loss, multi-comics allows for the merging and statistical analysis of DNA, RNA, proteins, epigenetic modifications and small and large molecules alongside clinical and epidemiological data.  This allows vast amounts of mulit-omics data generated from potential millions of biological samples for summarisation that enables biomarker prediction.  In simple terms, multi-comics can find the needle in the proverbial haystack.

Systems biology and hair loss
Systems biology and hair loss

WHAT DID THE STUDY FIND?

A multi-omics study completed by Michaletti in 2019 used a combination of proteomics and metabolomics to investigate the effect of keratin differentiation with different levels of calcium concentration [2].  Researchers used raw RNA sequences to analyse the effect of different concentrations of calcium in hair follicle cultures.

RNAs are used to copy genetic information from DNA for the synthesis of specific proteins that provide instructions for the cell.  Analysis of RNA sequences in response to calcium concentration gives a clear picture of the instructions given to a cell under different conditions.

It was found that protein expression was dependant on the concentration of calcium within the cell.  When calcium concentration was increased, proteins involved in cell adhesion, growth and maintenance were unregulated.

When there were lower levels of calcium, there were higher protein misfolding events that led to stress signals that induced early keratin cell death.  Also, higher levels of calcium led to beneficial differences in how DNA was translated and modifications after translation that led to increased keratin cell development.

Calcium and hair growth

Protein expression is dependant on calcium concentration within the cell. Higher levels of intracellular calcium increases cell adhesion contributing to stronger and longer hair.

CALCIUM INCREASES PROTEIN CONCENTRATION IN KERATIN CELLS

The protein concentration within the keratin cells that make up the hair fibre will determine the thickness of the final fibre as it emerges from the scalp.  Calcium is a major regulator of keratin cell differentiation.  The differentiation process of the keratin cell is where substantial changes happen within the cells.  After keratin cells grow and divide, they move up the hair follicle niche and then commit to differentiate from living cells to a hard and waterproof, fibrous material.

Depending upon the location of the keratin cell there are different keratin proteins and keratin associated proteins secreted.  These keratin proteins make up the cuticle, the cortex and surrounding proteins that make up the rest of the hair fibre.  Keratin-associated protein 1,2 and 3 make up the hair cortex and the cuticle is make up of keratin-associated protein 5 and 10.

Calcium promotes differentiation via signalling inside and outside of the cell.  The calcium receptor plays a central role that drives the differentiation response.  A high calcium concentration allows a higher expression of keratin in the surrounding cells.

Calcium and hair loss

Calcium increased the protein content of keratin cells. Higher levels of intracellular calcium increases keratin associated proteins 1, 2, 3, 5 and 10 within the hair fibre contributing to stronger hair.

CALCIUM INCREASES CELL ADHESION AND REDUCES PREMATURE HAIR SHEDDING

For the keratin cells that make up the hair fibre to continue to grow, the hair fibre must remained anchored to the base of the dermis (hypodermis or stratum basal).  The hypodermis contains collagen cells, lipids (fat) and there components that assist in hair fibre anchorage.

If the hair fibre can not remain anchored the keratin cells at the base of the follicle will stop the proliferation process and enter prematurely into the differentiation stage.  The hair fibre will also shed within 3 months of losing anchorage to the hypodermis.

Calcium supports cell-to-cell junctions for the support of cell adhesion.  The base of the hair follicle is made up of adherens junctions, tight junctions and desmosomes.  These contacts operate as important signalling complexes as well as sites of adhesion.  Calcium plays a critical role in enabling these intercellular contacts by maintaining the strength of these individual intercellular bonds.

CALCIUM INCREASES ANAGEN GENE EXPRESSION FOR A LONGER HAIR GROWTH CYCLE

Genes provide instructions provided for the cell using DNA as a template for new proteins.

Depending on the cells  status, a keratin cell may be instructed to keep growing or to stop growing.  Once the cell instructs the cells to stop growing, the hair fibre will prepare to detach from the hypodermis in preparation to be shed.

A cysteine-rich calcium binding protein, S100A3, has been shown to be highly expressed in growing hair cells in the cuticle layer.  A slightly lower level is observed in the keratin cells that make up the hair cortex. The level of S100A3 mRNA is elevated during the anagen phase of the hair growth cycle, and sharply declines when the hair follicle regresses into telogen phase.

The S100A3 gene is exclusively expressed in the keratin cells that make up major components of the hair fibre and demonstrates the essential calcium-dependant process that contributes to hair growth [3].

CALCIUM PROMOTES DNA REPAIR IN CELLS THAT MAKE UP THE HAIR FOLLICLE

DNA damage can occur in keratin cells due to high levels of oxidative damage from UVB rays or reactive oxygen species.  When damaged, DNA may undergo chemical alterations such as stand breaking, cross linking and the loss of DNA bases.  This damage can result in the loss of genetic information which leaves cells unable to produce the proteins necessary for cell survival.

For proteins produced by DNA transcription to be useful to a cell, the proteins need to be folded into the right configuration to work properly.

Damage to DNA can result in misfolded proteins that are completely useless to the cell.  Protein misfolding can also occur when there are other stressors that affect protein structure overwhelm a cell.

Calcium is able to activate m-caplain, a cytosolic protein that is involved in cellular processes such as DNA repair and assistance in DNA replication and transcription.  Moreover, the expression of heat shock proteins and RNA binding proteins (required for DNA transcription) is increased with higher levels of calcium.  Heat shock proteins are particularly beneficial to the cell as they are able to correctly fold misfolded proteins and enable these dysfunctional cells to be functional within the cell.

DNA is used as a template to create proteins that are needed for a living cell.  Proteins perform a diverse range of functions in cells by acting as enzymes, carriers and hormones.  Some proteins provide structural support for the cell.  Keratin cells produce a lot of keratin, damage to the sections of DNA reacting to keratin can reduce the amount of keratin within a keratin cell leading to weak and brittle hair.

INCREASING CALCIUM LEVELS WILL HELP MAINTAIN HAIR GROWTH

Higher intracellular calcium levels are shown to help with healthy development of the hair fibre.

Higher levels of calcium increase protein expressions that support keratin cell growth and maintenance. Calcium reducies protein misfolding events that can lead to impaired keratin cell development.

Get enough calcium in your diet – Consume calcium rich foods such as dairy foods, bread with fortified flour and green leafy vegetables such as spinach and curly kale.  According to the NHS, adults aged 19-64 need around 700mg of calcium per day.

Check your vitamin D levels – One of the main functions of vitamin D is to increase calcium absorption from the intestines.  According to Harvard Medical School, when you are low in vitamin D, you can only absorb around 10% of ingested calcium.

Eat a high zinc diet or take a supplement – Supplementing with zinc has been shown to increase levels of zinc by lowering the levels of vitamin D receptors on hair follicle membranes.

Zinc also helps the way cells use vitamin D to ensure maximum calcium absorption [4].

Top up your taurine – Taurine, a sulphur containing amino acid regulates calcium levels with a cell.  Taurine can be obtained from the diet and in the presence of vitamin B6 (pyridoxine) can be synthesised from cysteine and methionine.

REFERENCES

  1. Pillai, S., Bikle, D.D., Mancianti, M.L., Cline, P. and Hincenbergs, M., 1990. Calcium regulation of growth and differentiation of normal human keratinocytes: modulation of differentiation competence by stages of growth and extracellular calcium. Journal of cellular physiology, 143(2), pp.294-302.
  2. Michaletti, A., Mancini, M., Smirnov, A., Candi, E., Melino, G. and Zolla, L., 2019. Multi-omics profiling of calcium-induced human keratinocytes differentiation reveals modulation of unfolded protein response signaling pathways. Cell cycle, 18(17), pp.2124-2140.
  3. Shams, B., Afshari, E., Tajadini, M., Keikha, M., Qorbani, M., Heshmat, R., Motlagh, M.E. and Kelishadi, R., 2016. The relationship of serum vitamin D and Zinc in a nationally representative sample of Iranian children and adolescents: The CASPIAN-III study. Medical journal of the Islamic Republic of Iran, 30, p.430.

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